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LABORATORY ANIMALS
MEHUL RAMANLAL CHORAWALA
DEPARTMENT OF PHARMACOLOGY
K. B. INSTITUTE OF PHARMACEUTICAL
EDUCATION AND RESEARCH
A CONSTITUENT COLLEGE OF KADI SARVA VISHWAVIDYALAYA
GH-6, SECTOR-23
GANDHINAGAR-382023,
GUJARAT
Commonly used lab. animals
• Kingdom: Animalia
• Phylum: Chordata
• Class: Mammalia
• Most widely used:
• Mammals: Monkey, baboons, chimpanzees, cat,
dog, ferrets, shrew , gerbil, guinea pig, rat,
mouse, oppossum, mice
• Other less widely used:
• Birds, reptiles, amphibians, fish, shark
Almost all lab.
Animals belong to
mammalia class
Definitions
• Primates: Any member of the biological order
Primates, group that contains all lemurs, monkeys,
and apes, including humans.
• Carnivores: derives its energy and nutrient
requirements from a diet consisting mainly or
exclusively of animal tissue, whether through
predation or scavenging. (meat eater) Animals that
depend solely on animal flesh for their nutrient
requirements are considered obligate carnivores
while those that also consume non-animal food
are considered facultative carnivores .
– Insectivores: type of carnivore with a diet that consists
chiefly of insects and similar small creatures.
• Lagomorpha
• Chordata
Definitions
Definitions
• Rodents: “Rodere” meaning gnaw. two
continuously growing incisors in the upper
and lower jaws which must be kept short by
gnawing.
• 40 % of mammal species
• all continents other than Antarctica.
• include mice, rats, squirrels, porcupines,
beavers, chipmunks, guinea pigs, and voles.
• sharp incisors that they use to gnaw wood,
break into food, and bite predators.
• Eat stored food and spread disease
Difference between Lagomorpha & Rodentia
Lagomorpha Rodentia
• four incisors in the upper
jaw
• Almost wholly herbivorous
• Male's scrotum is in front of
the penis
• Penis contains no bone
(baculum)
• teeth grow throughout their
life, thus necessitating
constant chewing to keep
them from growing too long.
• E. g rabbit, hare
• Two in the Rodentia
• Many eat both meat
and vegetables
• Male's scrotum is
behind the penis
• Penis contains bone
(baculum)
• teeth grow throughout
their life .
• E. g mouse, rat, guinea
pig
Animals
– Rodents:
– Rat (Rattus norvegicus)
– Mouse (Mus musculus)
– Guinea pig (Cavia porcylus)
– Gerbil ()
– Hamster ()
– Didelphimorphs
• Opossum ()
– Insectivores
– Least shrew (Cryptotis parva)
– Asian musk shrew (Suncus murinus) (vomits-CTZ
ab.-Other brain area involved )
Animals
– Lagomorphs
– Rabbit (Oryctologus cuniculus)
– Carnivores:
– Dog ()
– Cat (Felis catus)
– Ferret ()
• Nonhuman primates:
– Rhesus monkey (Macaca mulatta)
– Crab-eating macaque (M. fascicularis or
cynomologus)
– Squirrel monkey (Saimiri sciureus)
Biological names
• Genus and species followed by variety
• Genus:
• Species:
• Breed:
• Strain:
• Variety:
• Breed and strain are from the same
species.
Species
• Almost all domestic pet rats and lab rats
belong to a single species, the Norway rat
(Rattus norvegicus).
• Wild black rats (Rattus rattus)
• rattus & norvegicus are species
• 66 species within genus : Rattus
Strain
• Group of individuals which share a presumed
common ancestry and have clear-cut
physiological but not usually morphological
distinctions
• Rat strains -- laboratory rats that have been
bred in isolation for generations.
• A rat strain is created through breeding
• Similar to each other and can therefore be
used in research.
• E. g Wistar, Fisher, and Sprague Dawley, and
their hundreds of internal divisions
Breed
• A type of animal that differs from all others
of the same species in some way, has a
separate history and breed name, and has
been breeding true for a number of
generations.
• Beagle and Doberman are examples of
different dog breeds.
• 1,000 dog breeds
• No separate breeds of rats
Breed Vs strain
• Overlap between the two terms
• Both refer to subgroups of individuals in a given species
which share common traits due to common descent.
• Strain → physiological differences
• Breed → morphological differences.
• Physiological differences → differences in physical and
chemical function, and therefore are often internal and
invisible.
• E. g a high resistance to cold or heat, a blood clotting
disorder, an immunodeficiency, high milk yield (cows),
strong wool (sheep)
• Morphological differences → differences in form or
function, and therefore tend to be external and visible.
• E. g body size, leg length, coat color, coat length, tail
length, head shape, and ear placement.
Variety
• Pet rats are quite variable in appearance –
– e. g different colors and markings
– Fur: straight or wavy or without fur
– Ears: may be low-set
– Tails: long or short or absent
• Rat variation is loosely divided into varieties or types (e.g.
RMCA and AFRMA).
• A variety : group of rats that share a single physical trait.
• E. g rats with curly fur belong to the "rex" variety, rats
with low-set ears are called "dumbo," rats without hair
are called "hairless."
• Single rat may belong to more than one variety, such
"dumbo" and "rex."
• A variety is therefore a purely descriptive category, it says
Varieties in rats
• All rats are shown in six Varieties:
STANDARD – With short, smooth, glossy hair
REX – With curly hair and curly whiskers
TAILLESS – Complete absence of a tail
HAIRLESS – Complete absence of hair
SATIN – Thinner, longer coat, with a lustrous
sheen
DUMBO – Larger ears set on the side of the
head
Varieties in rats (Rex)
Varieties in rats (Rex)
Varieties in rats (Dumbo Rat)
Varieties in rats (Satin Rat)
Satin Rat (Ivory)
Inbred strain
• Defined as a product of over 20 generations of
brother-sister matings, which results in individuals
that are 98% identical to each other.
• After 40 generations of inbreeding, they are 99.5%
similar. In other words, they are almost clones.
• At this stage, the inbreeding coefficient should be ∼
0.99 (i. e, residual heterozygosity approximately 1%).
• Animals of the same strain and sex are homozygous
and genetically very similar.
• The assumption that all sources of the same inbred
strain provide genetically identical animals is not
valid, as animals maintained at different institutions
for many generations may show genetic drift, even
though they originate from the same source.
Inbred strain
• Advantage
• remain genetically stable over a long period of time.
• However, it is important to be aware that the use of
inbred strains depends on the nature of the
experiments.
• Disadvantage
• Constant monitoring of the genetic stability of an
inbred strain is required.
• Each of them represents a very narrow selection of
the wide and functional genetic variation observed in
a wild population.
• The use of at least two inbred strains is often
preferable when toxicity studies are extrapolated to
human population.
Substrains
• They are subdivisions within a strain of rats.
• Substrain with an established genetic difference,
the substrain of Zucker rats (Lois M. Zucker and
Theodore F. Zucker, pioneer researchers in the
study of the genetics of obesity.)
• Leptin receptor in hypothalamus (satiety)
• Zucker -- Faulty leptin receptors. Leptin can't bind
to the faulty receptor, so Zucker rats never feel
full.
• Eat constantly and become morbidly obese
• As models for obesity, diabetes and heart disease
Zucker Fatty Rat
Diabetic Zucker Rat
Outbred Strain
• Genetically heterogeneous and are often
produced by breeding systems that
minimize inbreeding.
• Random pairing is best planned with the
aid of tables of randomized numbers or a
randomizing device.
Outbred Strain
• Disadvantages
• each breeding colony may be different due to
genetic drift.
• Wistar or Sprague - Dawley rat from one breeder
may be genotypically and phenotypically different
from those obtained from a different source.
• Considerable differences in neuroanatomy,
behaviour and pharmacology have been reported,
for example, in Sprague - Dawley rats obtained
from different commercial breeders.
Stock Vs Strain
• The term ‘ stock ’ is used to denote an
outbreed population of mice while the term ‘
strain ’ is used to denote an inbred
population.
• Defined as an outbreed when it has been
maintained as a closed colony for at least four
generations.
• To minimize changes caused by inbreeding
and genetic drift, the population should be
maintained in such numbers as to give less
than 1% inbreeding per generation.
Rattus
• Rattus contains 66 species
• Rattus norvegicus or brown Norway rat
• Rattus rattus or black rat
• The two species differ considerably in their
habitats, behavior and ecology.
• Wild Rattus norvegicus has agouti -coloured fur-
- has agouti gene which produces hairs with
colour bands varying between brown –black and
red – yellow.
• Rattus rattus may have a more variable coat
colour, but is mainly dark brown or black.
• R. norvegicus lives mainly in burrow systems at
ground level, whereas R. rattus tend to occupy
higher areas in trees and roofs.
History of the Norway Rat (R. norvegicus)
• The first laboratory rats:
• Albino rats (actually spontaneous mutation was seen)
were brought into laboratories for physiological
studies as early as 1828.
• First breeding experiments in the 1870s and 1880s
• White rats of European origin were brought to
America shortly after this and became the foundation
stock of American laboratory rats
• The oldest strain of inbred rats dates from 1856.
• The oldest purpose-bred strain of inbred rats, the PA
strain, had been created by Helen Dean King at the
Wistar institute in Philadelphia by 1909 .
• The Wistar rat, and to a lesser extent, the Sprague-
Dawley rat, gradually became the most popular rat
strains for laboratory research.
Laboratory rat
• A laboratory rat is a rat of the species Rattus norvegicus
which is bred and kept for scientific research.
• Laboratory rats have served as an important animal
model for research in psychology, medicine, and other
fields.
Comparison and contrast between
• RAT : Wistar and Sprague Dawley Strains
• Common name : Rat
• Scientific name : Rattus norvegicus
• Strain : Wistar and Sprague Dawley
• Source: Denmark
• Coat color: Albino
Comparison and contrast between
• Wistar rats → wider head, long ears, and
the tail length always shorter than that of
the body length.
• Sprague - Dawley rats→ longer and
narrower in head , longer tail, which may
equal or be longer than the body length.
• Wistar rats are more active than Sprague
Dawley rats
Strains of lab. rats
• Albino Wistar :
• Developed at the Wistar Institute in
1906.
• Easy to handle and male aggressive
behavior develops relatively late.
• An outbred or random - bred strain
and a large number of varieties exist
worldwide.
Strains of lab. rats
• Albino Sprague - Dawley :
 Originated by R. Dawley, Sprague-Dawley Company,
Madison, Wisconsin, in 1925.
 Now purchased by Harlan Sprague Dawley
 Originally female albino Wistar rats were crossed
with hybrid hooded males from an unknown origin.
and subsequently to his white female offspring for
seven successive generations.
 Multiple lines, developed by inbreeding,
 thereafter were outbred to develop a stable,
heterogeneous stock.
 Calmness and ease of handling
Sprague dowley
Sprague dowley Rats
Strains of lab. rat
• Long - Evans hooded:
• Developed by Dr. Long & Evans at Berkeley,
California in 1910.
• Crossing several Wistar females with wild
gray male.
• Head and extremities - black or brown
• Rest of the body - white with pigmented
eyes
• easily handled
• Level of aggressive behavior is generally
high.
• Behavioral and obesity research
Long Evans Rat
Long Evans Rat
Uncommon strains or substrains
• Apart from the traditional inbred and outbred strains, a wide
variety of genetic selection lines are available. These lines are
genetically selected for the presence or absence of certain
behavioural or physiological characteristics.
• E. g Roman High Avoidance (RHA) and Roman Low Avoidance
(RLA) lines are selected for their behavioral performance in an
active shock avoidance paradigm, using the Roman Wistar as the
parental population.
• The Kyoto Wistar was used to select the Spontaneous
Hypertensive Rat (SHR) line, using high sympathetic reactivity as
a selection criterion.
• Most of these genetic selection lines are not commercially
available
• Can only be obtained via the specific research institutes that
breed and select these lines.
Shaking rat Kawasaki
• Neurological mutant rat in the Wistar strain first described in 1988:
• Neurological signs : shaking of the body and an ataxic-paretic gait from
day 10 postnatal.
• CNS: cerebellum: small, frequently vermis and paraflocculus lacking,
malposition of the neurons in the cerebral cortex, hippocampus and
cerebellum.
• Abnormal myelinated fibers in the molecular layer of the cerebral
cortex and in the central gray matter of the spinal cord.
• Survival : The affected rats survive for about 1 month.
• Genes : short deletion in the RELN gene; Reelin, product of RELN gene
is essential for proper cortex lamination and cerebellum development.
• good animal model of human congenital malformations with neuronal
migration disorders.
RCS rats
• The Royal College of Surgeons (RCS) rat
• The first known animal with inherited
retinal degeneration.
• Mutation in the gene Mertk results in
defective retinal pigment epithelium
Hairless rats
• compromised immune systems and genetic kidney diseases
• Over 25 genes that cause recessive hairlessness in laboratory rats
• Common : rnu (Rowett nude), fz (fuzzy) and shn (shorn).
• Rowett nudes, first identified in 1953 in Scotland, have no thymus.
• severely compromises their immune system, infections of the RT and
eye increasing the most dramatically.
• Fuzzy rats (fz/fz rats) were identified in 1976 in a Pennsylvanian
lab.
• progressive kidney failure that begins around the age of one month
causes death.
• Shorn rats were bred from Sprague Dawley rats in Connecticut in
1998.
• They also suffer from severe kidney problems.
Hairless rats
Fuzzy rats
• fuzzy mutation has been mapped to a location on Chromosome 1
Homozygous infant rats have curly or twisted whiskers at birth. First
coat is short, rough, and the hairs are broken, which gives the coat a
wavy appearance.
• This short coat may last through one or two hair cycles, but by 2
months of age most mutant rats have only sparse hair and a fuzzy
appearance, or no hair at all.
• By six months, all homozygous rats are usually smooth-skinned and
remain so thereafter.
• suffers from chronic, progressive nephrosis, or nephropathy, which
shortened their lifespan to 16.6 months in males and 20.4 months in
females.
• Males averaged 16.6 months (range: 12-20 months), and females
averaged 20.4 months (range: 17-26 months) at time of death.
• decreased lifespan as compare to normal rats
Shorn rats
• The shorn locus has been mapped to a narrow
area of Chromosome 7
• Shorn, a recessive mutation causing hairlessness,
was discovered in 1993.
• Shorn rats display a very sparse, patchy coat
throughout their lifetimes.
• develop abnormal hearts and kidneys which are
yellow and bumpy instead of red and smooth.
• tend to be smaller than normal rats and they die
prematurely, at around 12-14 months of age
Orthologues between rat and
mouse genes causing hairlessness
Rats Mice
fuzzy (fz), Charles River hairless (hr) frizzy (fr)
Rowlett Nude (rnu), New Zealand Nude
(nznu)
nude
(Whn)
shorn (shn) -- none --
-- none -- fuzzy (fz)
-- none --
hairless
(hr)
Biobreeding Rat (BB)
• Known as BB or BBDP rat is an inbred laboratory rat strain
that spontaneously develops autoimmune Type 1 Diabetes.
• BB rats are used as an animal model for Type 1 diabetes.
The strain re-capitulates many of the features of human
type 1 diabetes, and has contributed greatly to the research
of T1D pathogenesis.
• Two genes have been identified - the MHC Class II gene and
Gimap5, causing a severe T cell lymphopenia.
• Recently, 8 further loci on rat chromosomes 1,2,3,6 (2 loci),
12 and 14 have been shown to be linked to Type 1 Diabetes
in the BB rat.
• Non-obese diabetic or NOD mice, like the Biobreeding rat,
are used as an animal model for type 1 diabetes. NOD mice
exhibit a susceptibility to spontaneous development of
autoimmune insulin dependent diabetes mellitus...
Why rats can’t vomit ?
• Rats have a powerful and effective gastroesophageal barrier
(1) Rats can't relax the crural sling while contracting the rest of
the diaphragm.
– The diaphragm has two muscles: the crural (muscle fibers attached to
the vertebrae, called the crural sling) and the costal (muscle fibers
attached to the rib cage). For vomiting costal muscle contraction and
crural muscle relaxation required. Doesn’t occur in rat.
(2) they can't wrench open the esophageal sphincter.
– esophageal sphincter is opened during vomiting with the help of the
longitudinal muscle of the esophagus. Weak in rat.
(3) rats lack the necessary neural connections to coordinate the
muscles involved in vomiting.
– Brainstem nuclei and the muscle systems used in vomiting, rats don’t
have complex connections between the nuclei or between the
brainstem and the viscera that are required for such a coordinated
behavior. E. g Rat, mouse, guinea pig, rabbit
Alternative to vomiting
• Rats do experience nausea and have evolved
an alternative to vomiting:
• pica, the consumption of non-nutritive
substances
• When rats feel nauseous they eat things like
clay, kaolin, dirt and even hardwood bedding
(eating clay and dirt is a type of pica called
geophagia).
• Clay -- binds and inactivates chemicals so
deactivates toxins.
• Food avoidance Response- First line defence
• Pica -- second line of defense against toxins.
kangaroo rats
• Norway rats, kangaroo rats, and cotton rats all look like
"rats" to the casual eye, even though they have many other
subtle differences that indicate they are not as closely
related as they look.
• Their resemblance to each other is actually only superficial
-- they're all rodents with long tails,
• Kangaroo rats are only distantly related to Norway rats.
• They are both rodent species (they belong to the order
Rodentia)
• Kangaroo rats belong to the family Heteromyidae, while
Norway rats belong to a different family called Muridae.
• In fact, Norway rats are more closely related to house mice
than they are to kangaroo rats, as both rats and mice
belong to the same family Muridae.
• Kingdom: Animalia
• Phylum: Chordata
• Class: Mammalia
• Order: Rodentia
• Family: Heteromyidae
• Subfamily: Dipodomyinae
• Genus: Dipodomys
Kangaroo Rat
Kangaroo Rat
Characteristics of Kangaroo rat
• 19 species
• Size : 10 to 20 cm, with a tail of equal or slightly greater length
• Weight : 35 to 180 grams
• Most distinctive features: very long hind legs & efficient kidneys.
• Longer loop of Henle in the nephrons which permit a greater
magnitude of countercurrent multiplication , can produce urine up
to an osmolarity of almost 6,000 mosm/liter, which is five times
more concentrated than maximally concentrated human urine at
1,200 mosm/liter.
• Because of this tremendous concentration ability, kangaroo rats
never have to drink; the water produced metabolically within their
cells during oxidation of foodstuff (food plus O2 yields CO2 + H2O +
energy) is sufficient for their body.
• Don’t lose water by perspiring because have no sweat glands.
• Can recover 90% of the loss by using metabolic water gaining the
remaining 10% from the small amount of water in their diet.
Kangaroo rat
Cotton Rat
• Cotton Rat Origin
• In 1996, Harlan obtained a cotton rat breeding
nucleus from National Institutes of Health,
Bethesda, Maryland, and Virion Systems, Inc.
• Any member of the rodent having genus
Sigmodon.
• build their nests out of cotton, and can damage
cotton crops.
• small ears and dark coats
• North and South America
• primarily herbivores
• Cotton rats are a little more closely related to
Norway rats.
• They belong to the same family Muridae, but
cotton rats are in a different genus, called
Sigmodon, while Norway rats are in the genus
Rattus.
• Molars of cotton rats are S-shaped when
viewed from above (genus- meaning S-
tooth).
• Sigmodon hispidus was the first model
organism to be used in polio research.
Cotton Rat
Biological Classification
• Kingdom: Animalia
• Phylum: Chordata
• Class: Mammalia
• Order: Rodentia
• Family: Cricetidae
• Subfamily: Sigmodontinae
• Tribe: Sigmodontini Wagner, 1843
• Genus: Sigmodon
Cotton rat (hispidicus)
Cotton Rat Characteristics
• Coat: color combination varies; gray,
brown, black
• Litter average: 5.5
• New World rodent: Sigmodon hispidus
• Susceptible to a wide range of human
infectious disease agents
Cotton rats as model of infectious diseases
Adenoviral vector-based gene therapy
Infectious disease pathogenesis
• Respiratory Syncytial Virus
• Herpes Simplex (Type 1 & Type 2)
• Parainfluenza Type 3
• Polio
• Measles
• Monkeypox
• Metapneumovirus
• Human Immunodeficiency Virus
• Influenza Virus
Cotton rats as model of infectious
diseases
Bacterial infections
– Mycobyterium tuberculosis bovis
– Haemophilus influenzae
– Rickettsial infections
– Staphylococcus aureus
Fungal infections
Parasitic infections
Hamster
• Kingdom: Animalia
• Phylum: Chordata
• Subphylum: Vertebrata
• Class: Mammalia
• Order: Rodentia
• Suborder: Myomorpha
• Superfamily: Muroidea
• Family: Cricetidae
• Subfamily: Cricetinae
• Genera: Mesocricetus, Phodopus, Cricetus,
Cricetulus, Allocricetulus, Cansumys, Tscherskia
• 25 species
Hamsters
• Stout - bodied, stubby – tailed, virtually tailless, broad - headed,
velvet-furred , cheek - pouched, burrowing and nest building
rodents.
• Origin: Middle East and Southeastern Europe
• Commonly used:
• Syrian hamster ( Mesocricetus auratus ),
known also as Golden Hamster
• Less often used:
• Chinese (Cricetus griseus )
• European hamsters (Cricetus cricetus )
• Djungarian hamster (Phodopus sungorus), also known as the
Winter white Russian dwarf hamster, Dzungarian dwarf
hamster, Russian dwarf hamsters, Siberian hamster, Winter
white hamsters, and Sapphire winter white Russian dwarf
hamster
Hamsters characteristics
• Color and hair-type: cinnamon, cream, white, and
"teddy bear" (the long-haired variety).
• Unique anatomic feature of hamster:
• 1. cheek pouches =pouching of the oral (mouth) cavity on both
sides, extending alongside the head and neck to the shoulders.
• Use : to store food and allow the hamster to transport food
from where it is gathered to the hamster's den or nest. The
food is then eaten later, at the hamster's leisure.
• Represents false appearnace of tumors or abscesses.
• 2. paired glands in the skin over the flanks:
• Appear as dark spots within the haircoat and are much more
obvious in males than females.
• Glands are used to mark a hamster's territory and also have a
role in sexual behavior.
Syrian/Golden hamster
Syrian/Golden hamster
Syrian/Golden hamster
Golden Hamster
• Unusual and unique features which make them particularly
useful for certain experimental studies.
• Immuno – genetic characteristics : marked tolerance to
homologous, heterologous and human tumours, parasites,
viruses and bacteria.
• Reversible cheek pouches: allow tumour grafts from other
species, including man, to grow freely and symmetrically
without the need to induce immunosuppression.
• Dental research: form and occlusion of their molar teeth
closely resemble those of humans and the induction of
lesions is possible without fracturing of the teeth, as in rats.
• Teratology: short gestation period is advantageous
• Thermophysiology and circadian rhythm studies
• Use of Syrian hamster oocyte in assessing human
spermatozoal fertilising potential. Quantifying the effects of
various factors affecting human sperm function in vivo.
Chinese Hamster
Chinese Hamster with Pups
European hamster
Laboratory mouse
• most widely used vertebrate species in
biomedical research
• Adv:
– short reproductive cycle,
– Short lifespan,
– small size
– low cost of maintenance
• cancer and drug research, vaccine and
monoclonal antibody preparation and
evaluation of the safety and effectiveness of
pharmaceutical products.
Inbred mice
• Immunology
• Oncology
• Microbiology
• Biochemistry
• Pharmacology
• Physiology
• Anatomy
• Radiobiology
• offer a high degree of genetic uniformity
Dog
• Kingdom: Animalia
• Phylum: Chordata
• Class: Mammalia
• Order: Carnivora
• Family: Canidae
• Genus: Canis
• Species: C. lupus
• Subspecies: C. l. familiaris and C. l. dingo
Beagle dog
Beagle dog
Beagle dog
Beagle dog with puppy
Mongrel dogs
Use of dog
• dog genome is similar in size to the
genomes of humans and other mammals,
containing an estimated 2.8 billion DNA
base pairs.
• excellent model for researching numerous
diseases requiring subtle phenotyping
• many breeds of dogs are prone to genetic
diseases including cancer and autoimmune
disorders that are difficult to study in
humans
Ferrets
• Kingdom: Animalia
• Phylum: Chordata
• Class: Mammalia
• Order: Carnivora
• Family: Mustelidae
• Genus: Mustela
• Species: M. putorius
• Subspecies: M. p. furo
Ferrets
Dentition
• 4 types of teeth (the number includes maxillary
(upper) and mandibular (lower) teeth)
• 12 small teeth incisors (only a couple of mm)
located between the canines in the front of the
mouth. used for grooming.
• 4 canines used for killing prey.
• 12 premolar—located at the sides of the mouth,
directly behind the canines. The ferret uses these
teeth to cut through flesh, using them in a scissors
action to cut the meat into digestible chunks and
to chew food
• 6 molars (two on top and four on the bottom) at
the far back of the mouth are used to crush food.
Dentition of ferret
Uses of ferrets
• Share many anatomical and physiological features with
humans
• virology, reproductive physiology, anatomy,
endocrinology, and neuroscience
• Experimental animal model for human influenza
• Used to study the 2009 H1N1 (swine flu) virus
• Smith, Andrews, Laidlaw (1933) inoculated ferrets
intra-nasally with human naso-pharyngeal washes,
which produced a form of influenza that spread to
other cage mates.
• pathogenesis and treatment in a variety of human
disease e. g cardiovascular disease, nutrition
• Respiratory diseases such as SARS and human
influenza, airway physiology, cystic fibrosis and
gastrointestinal disease.
• Study all aspects of canine distemper, a
serious and fatal disease of dogs and many
forms of wildlife.
• Behavioral research: suited to certain
studies regarding learned behaviors.
• Neuroendocrinology studies : domesticated
species whose estrous cycle in the female is
easily monitored so an important animal
model for reproduction research
• Alternative to the use of dogs and non-
human primates in toxicology studies.
Uses of ferrets
Mongolian gerbil
• Kingdom: Animalia
• Phylum: Chordata
• Class: Mammalia
• Order: Rodentia
• Family: Muridae
• Subfamily: Gerbillinae
• Genus: Meriones
• Subgenus: Pallasiomys
• Biological name: Meriones unguiculatus
Mongolian gerbil
• known as the jird, clawed jird, sand rat, or
desert rat.
• Native to China and Mongolia
• Introduced into the US in 1954.
• The most common color is the agouti,
shown here: light buff to white ventrum,
with mixed white, yellow and black hairs
dorsally, giving an overall brown fur color.
Gerbils
Mongolian Gerbil
Gerbils
Pups of Gerbil
Behavior
• usually nonaggressive, curious and social.
• If a gerbil escapes, it does not attempt to hide
as other rodents do and will often return to
its cage.
• Nocturnal: most active in the evening with
cycles of activity during the day.
• Gerbils may form stable, monogamous pairs
and the male may assist the female in rearing
young.
• When they are excited or agitated they may
audibly stomp their large hindlimbs.
Uses of Mongolian gerbil
• Avg life : 3-4 years
• Good capacity for temperature regulation
• High incidence of spontaneous neoplasms with
increasing frequency in aging animals (≥ 2 year).
So unsuitable for chronic toxicity studies.
• Malignancies involving the ovaries, ventral
sebaceous glands, kidney, adrenal glands and skin.
• Abdominal sebaceous gland pad in the gerbil is
androgen dependent and readily observable
Uses
• Radiation studies: because they can tolerate much greater
whole-body radiation exposure than other animal species.
• Endocrine gland metabolism studies: one of the largest
ratios of adrenal weight to body weight of all animals.
• Experimental atherosclerosis
• Valuable animal model for stroke research. Most animal
species have a major arterial vascular supply to the base of
the brain - the Circle of Willis. This circle is incomplete in
the gerbil. Unilateral carotid ligation in the gerbil results in
ipsilateral cerebral ischemia.
• High incidence of spontaneous epileptiform seizures,
usually precipitated by a novel environment.
• Parasitology research- successfully infected with parasites
common to other species
Uses of Gerbil
• Lipid metabolism: display lipemia and
hypercholesterolemia even on rodent diets with
standard fat composition. this results in hepatic
lipidosis and gallstones, but not in atherosclerosis.
• Reproduction studies to evaluate antifertility drugs
• Auditory research: hearing curve is closer to man's
than most common laboratory animals.
• Psychology studies: due to exploratory and territorial
marking behaviors
• Toxicology research: studies of food additives,
pesticides, industrial solvents and heavy metals.
• Infectious disease research:
• Kingdom: Animalia
• Phylum: Chordata
• lass: Mammalia
• Order: Lagomorpha
• Family: Leporidae
• Genus: Oryctolagus Lilljeborg, 1873
• Species: O. cuniculus
Rabbits
Rabbits
• small mammals
• 8 different genera in the family classified as rabbits,
including
• European rabbit (Oryctolagus cuniculus),
• Cottontail rabbits (genus Sylvilagus; 13 species),
• Amami rabbit (Pentalagus furnessi, an endangered species
on Amami Ōshima, Japan).
• There are many other species of rabbit, and these, along
with pikas and hares, make up the order Lagomorpha.
• two living families, the Leporidae (hares and rabbits), and
the Ochotonidae (pikas).
• The male -- buck
• The female – doe
• young rabbit is a kitten or kit
Rabbits
• Use is declined over the last decade because of gradual
and slight decline of the use of polyclonal antibodies
produced in rabbits
• Polyclonal antibodies still required bec’ they are
quicker and easier to produce than the monoclonal
antibodies
• Pyrogen testing of intravenous fluids and other technical
products intended for patients even though other test
methods without live animals are being evaluated
• Development of bio implant products such as dental
implants and devices for orthopaedic surgery
• Study of atherosclerosis after being given high - fat and
high - cholesterol diets, which lead to the development
of atherosclerotic lesions in the major arteries after
approximately 2 months.
Rabbits
• WHHL (Watanabe heritable hyperlipidaemic):
Spontaneously mutated strain develop
atherosclerotic lesions in their blood vessels
even without the high - fat diet
• Toxicology: detection of teratogenic effects of
drugs because the embryological development of
the rabbit foetus is well known, the gestation
period is short and rabbits produce a fairly large
number of offspring
• Experimental teratology
• Cardiac surgery and disease, joint surgery,
ophthalmology and studies of hypertension
Opossum
• Kingdom: Animalia
• Phylum: Chordata
• Class: Mammalia
• Order: Didelphimorphia
• Family: Didelphidae
• Subfamily: Didelphinae
• Genus: Monodelphis
• Species: M. domestica
Order: Didelphimorphia
• small to medium-sized marsupials, with the largest just exceeding
the size of a large house cat, and the smallest the size of a small
mouse.
• semi-arboreal (often inhabiting and frequenting trees but not
completely arboreal =in burrows)
• omnivores (eat everything), although there are many exceptions.
• Most members of this taxon have long snouts (projecting nose,
jaws, or anterior facial part of an animal's head.),
• a narrow braincase,
• Prominent sagittal crest (ridge of bone running lengthwise along
the midline of the top of the skull (at the sagittal suture) of many
mammalian and reptilian skulls).
• dental formula is : 5.1.3.4: 4.1.3.4
• By mammalian standards, this is a very full jaw. The incisors are very
small, the canines large, and the molars are tricuspid.
Opossum
• Gray short-tailed opossum (Monodelphis
domestica)
• Small member of the Didelphidae family
• Possum = white dog
• The first marsupial to have its genome sequenced.
• Marsupiam: fold of skin, supported by epipubic
bones, containing the mammary glands into which
young ones are placed.
• Habitat: Bolivia , Brazil and Paraguay
• Frequently found in the exotic pet trade
• Biomedical research
• Also known as the Brazilian opossum, rainforest
opossum and in a research setting the laboratory
opossum.
Opossum
Opossum
• Readily available animals
• Suited for use in studies of
– Melanoma
– Hypercholesterolemia
– Development of arteriosclerosis, angiogenesis and
corneal cancer because they are altricial,
– Developmental studies are also done on their
extremely immature young.
– An increasing number of researchers are using the
laboratory opossum and considerable baseline data
are now available.
– M. domestica are easily cared for in standard rodent
cages and can be fed standard pelleted fox laboratory
diet.
Primates
• Primates:
• Primates should only be used in research
programmes where there is particular need
in justified research programmes and
where it can be demonstrated that the
benefits to society outweigh the harms
inflicted on the animals that are used.
Cat (Felis catus)
• Kingdom: Animalia
• Phylum: Chordata
• Class: Mammalia
• Order: Carnivora
• Family: Felidae
• Genus: Felis
• Species: F. catus
Primates
• The total number of primates used in
research worldwide is estimated at between
100 000 and 200 000, with 64.7% involving
Old World monkeys
• Most (up to 70 %) are used in regulatory
toxicology.
• The most common research areas for which
primates are used are:
– infectious diseases (including HIV/AIDS) 26%
– neuroscience 19 %
– biochemistry 12 %
– pharmacology/physiology 11 %
New and old World monkeys
• New World monkeys
• E. g Squirrel monkey, marmoset
• Native to Central and South America belong
to family : Callitrichidae, Cebidae, Aotidae,
Pitheciidae, and Atelidae
• Old World monkeys
• E. g Rhesus monkey
• Native to Africa and Asia belong to family :
Cercopithecidae
Rhesus monkey
• Rhesus Macaque (Macaca mulatta), also
called the Rhesus Monkey
• One of the best known species of Old World
monkeys.
• Kingdom: Animalia
• Phylum: Chordata
• Class: Mammalia
• Order: Primates
• Family: Cercopithecidae
• Genus: Macaca
• Species: M. mulatta
Rhesus monkey
Rhesus monkey
Squirrel monkey
• Squirrel monkeys and marmosets share many physical
characteristics, including small size and ease of handling that
contribute to their desirability as research subjects.
• Squirrel monkeys ( Saimiri spp.) -- most commonly used
neotropical primates in US.
• Europe – marmoset is used
• Adv:
• The mean body weight of adult squirrel monkeys is less than 1
kg compared with female rhesus monkeys, which usually
weigh 4 – 5 kg.
• Smaller doses necessary sp. Expensive medications
• easily adapt to laboratory housing
Squirrel monkey
Advs. of squirrel monkey
• smaller spaces and less expensive cages req’ than larger
primates, such as macaques and baboons.
• Less risk of serious zoonotic disease transmission with
squirrel monkeys and other neotropical primates than with
macaques and other Old World primates.
• Accidental exposures from bites and scratches can be
managed in a manner similar to those from dogs and cats,
and personal protective equipment required for handling
squirrel monkeys is less extensive.
• Reduced risk to laboratory workers combined with ease of
handling, allow more procedures to be carried out without
chemical restraint or expensive handling equipment.
• Easily habituated to handling, which further reduces stress
from manipulation.
• Experimental procedures that must be performed without
sedation can be carried out relatively easily in squirrel
monkeys.
Research models of squirrel monkey
• Physiological studies of the effects of space
flight -- ability to tolerate high gravitational
forces
• Atherosclerosis research-
– Wild squirrel monkeys also have naturally
occurring atherosclerotic lesions; fatty streaks
and plaques in aortas resembling human
atherosclerosis in lab. monkeys
• Experimental induction of cholelithiasis
• Reproductive biology
Research models of squirrel monkey
• malaria vaccine development studies-
important animal model
• Plasmodium spp. are host specific; therefore
the animals used for studies of human
malaria must be susceptible to the same
strains of Plasmodium that cause disease in
humans.
• The Bolivian squirrel monkey are superior
model than the Guyanese squirrel monkeys
(S. sciureus sciureus) P. Falciparum
• One of the most susceptible non -human primate
species to experimental infection with Creutzfeldt -
Jakob disease (CJD)
• Transmissible spongiform encephalopathies
Research models of squirrel monkey
Transgenic animals
• Genetically engineered or modifi ed mice are those
with induced mutations, including mice with
transgenes, with targeted mutations (knockouts)
and with retroviral, proviral or chemically induced
mutations .
• Transgenic technology focuses on the introduction
or exclusion (knockouts) of functional genetic
material in the germ line of an animal, thus
changing the genetic characteristics of an organism
and its progeny.
• The most frequently used methods for genetic
transformation of the germ line are microinjection of
DNA into the pro nucleus of fertilized oocytes and the
injection of transfected embryonic stem (ES) cells into
normal mouse blastocysts, resulting in a subsequent
generation of chimeras.
• These techniques have led to the rapid development
of a variety of animal models, designed for the study
of gene regulation, gene expression, pathogenesis
and the treatment of human and animal diseases (eg,
Alzheimer ’ s disease, growth hormone disturbances,
poliovirus vaccine testing ).
Transgenic animals

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Laboratory animals

  • 1. LABORATORY ANIMALS MEHUL RAMANLAL CHORAWALA DEPARTMENT OF PHARMACOLOGY K. B. INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH A CONSTITUENT COLLEGE OF KADI SARVA VISHWAVIDYALAYA GH-6, SECTOR-23 GANDHINAGAR-382023, GUJARAT
  • 2. Commonly used lab. animals • Kingdom: Animalia • Phylum: Chordata • Class: Mammalia • Most widely used: • Mammals: Monkey, baboons, chimpanzees, cat, dog, ferrets, shrew , gerbil, guinea pig, rat, mouse, oppossum, mice • Other less widely used: • Birds, reptiles, amphibians, fish, shark Almost all lab. Animals belong to mammalia class
  • 3. Definitions • Primates: Any member of the biological order Primates, group that contains all lemurs, monkeys, and apes, including humans. • Carnivores: derives its energy and nutrient requirements from a diet consisting mainly or exclusively of animal tissue, whether through predation or scavenging. (meat eater) Animals that depend solely on animal flesh for their nutrient requirements are considered obligate carnivores while those that also consume non-animal food are considered facultative carnivores . – Insectivores: type of carnivore with a diet that consists chiefly of insects and similar small creatures.
  • 5. Definitions • Rodents: “Rodere” meaning gnaw. two continuously growing incisors in the upper and lower jaws which must be kept short by gnawing. • 40 % of mammal species • all continents other than Antarctica. • include mice, rats, squirrels, porcupines, beavers, chipmunks, guinea pigs, and voles. • sharp incisors that they use to gnaw wood, break into food, and bite predators. • Eat stored food and spread disease
  • 6. Difference between Lagomorpha & Rodentia Lagomorpha Rodentia • four incisors in the upper jaw • Almost wholly herbivorous • Male's scrotum is in front of the penis • Penis contains no bone (baculum) • teeth grow throughout their life, thus necessitating constant chewing to keep them from growing too long. • E. g rabbit, hare • Two in the Rodentia • Many eat both meat and vegetables • Male's scrotum is behind the penis • Penis contains bone (baculum) • teeth grow throughout their life . • E. g mouse, rat, guinea pig
  • 7. Animals – Rodents: – Rat (Rattus norvegicus) – Mouse (Mus musculus) – Guinea pig (Cavia porcylus) – Gerbil () – Hamster () – Didelphimorphs • Opossum () – Insectivores – Least shrew (Cryptotis parva) – Asian musk shrew (Suncus murinus) (vomits-CTZ ab.-Other brain area involved )
  • 8. Animals – Lagomorphs – Rabbit (Oryctologus cuniculus) – Carnivores: – Dog () – Cat (Felis catus) – Ferret () • Nonhuman primates: – Rhesus monkey (Macaca mulatta) – Crab-eating macaque (M. fascicularis or cynomologus) – Squirrel monkey (Saimiri sciureus)
  • 9. Biological names • Genus and species followed by variety • Genus: • Species: • Breed: • Strain: • Variety: • Breed and strain are from the same species.
  • 10. Species • Almost all domestic pet rats and lab rats belong to a single species, the Norway rat (Rattus norvegicus). • Wild black rats (Rattus rattus) • rattus & norvegicus are species • 66 species within genus : Rattus
  • 11. Strain • Group of individuals which share a presumed common ancestry and have clear-cut physiological but not usually morphological distinctions • Rat strains -- laboratory rats that have been bred in isolation for generations. • A rat strain is created through breeding • Similar to each other and can therefore be used in research. • E. g Wistar, Fisher, and Sprague Dawley, and their hundreds of internal divisions
  • 12. Breed • A type of animal that differs from all others of the same species in some way, has a separate history and breed name, and has been breeding true for a number of generations. • Beagle and Doberman are examples of different dog breeds. • 1,000 dog breeds • No separate breeds of rats
  • 13. Breed Vs strain • Overlap between the two terms • Both refer to subgroups of individuals in a given species which share common traits due to common descent. • Strain → physiological differences • Breed → morphological differences. • Physiological differences → differences in physical and chemical function, and therefore are often internal and invisible. • E. g a high resistance to cold or heat, a blood clotting disorder, an immunodeficiency, high milk yield (cows), strong wool (sheep) • Morphological differences → differences in form or function, and therefore tend to be external and visible. • E. g body size, leg length, coat color, coat length, tail length, head shape, and ear placement.
  • 14. Variety • Pet rats are quite variable in appearance – – e. g different colors and markings – Fur: straight or wavy or without fur – Ears: may be low-set – Tails: long or short or absent • Rat variation is loosely divided into varieties or types (e.g. RMCA and AFRMA). • A variety : group of rats that share a single physical trait. • E. g rats with curly fur belong to the "rex" variety, rats with low-set ears are called "dumbo," rats without hair are called "hairless." • Single rat may belong to more than one variety, such "dumbo" and "rex." • A variety is therefore a purely descriptive category, it says
  • 15. Varieties in rats • All rats are shown in six Varieties: STANDARD – With short, smooth, glossy hair REX – With curly hair and curly whiskers TAILLESS – Complete absence of a tail HAIRLESS – Complete absence of hair SATIN – Thinner, longer coat, with a lustrous sheen DUMBO – Larger ears set on the side of the head
  • 18. Varieties in rats (Dumbo Rat)
  • 19. Varieties in rats (Satin Rat)
  • 21. Inbred strain • Defined as a product of over 20 generations of brother-sister matings, which results in individuals that are 98% identical to each other. • After 40 generations of inbreeding, they are 99.5% similar. In other words, they are almost clones. • At this stage, the inbreeding coefficient should be ∼ 0.99 (i. e, residual heterozygosity approximately 1%). • Animals of the same strain and sex are homozygous and genetically very similar. • The assumption that all sources of the same inbred strain provide genetically identical animals is not valid, as animals maintained at different institutions for many generations may show genetic drift, even though they originate from the same source.
  • 22. Inbred strain • Advantage • remain genetically stable over a long period of time. • However, it is important to be aware that the use of inbred strains depends on the nature of the experiments. • Disadvantage • Constant monitoring of the genetic stability of an inbred strain is required. • Each of them represents a very narrow selection of the wide and functional genetic variation observed in a wild population. • The use of at least two inbred strains is often preferable when toxicity studies are extrapolated to human population.
  • 23. Substrains • They are subdivisions within a strain of rats. • Substrain with an established genetic difference, the substrain of Zucker rats (Lois M. Zucker and Theodore F. Zucker, pioneer researchers in the study of the genetics of obesity.) • Leptin receptor in hypothalamus (satiety) • Zucker -- Faulty leptin receptors. Leptin can't bind to the faulty receptor, so Zucker rats never feel full. • Eat constantly and become morbidly obese • As models for obesity, diabetes and heart disease
  • 26. Outbred Strain • Genetically heterogeneous and are often produced by breeding systems that minimize inbreeding. • Random pairing is best planned with the aid of tables of randomized numbers or a randomizing device.
  • 27. Outbred Strain • Disadvantages • each breeding colony may be different due to genetic drift. • Wistar or Sprague - Dawley rat from one breeder may be genotypically and phenotypically different from those obtained from a different source. • Considerable differences in neuroanatomy, behaviour and pharmacology have been reported, for example, in Sprague - Dawley rats obtained from different commercial breeders.
  • 28. Stock Vs Strain • The term ‘ stock ’ is used to denote an outbreed population of mice while the term ‘ strain ’ is used to denote an inbred population. • Defined as an outbreed when it has been maintained as a closed colony for at least four generations. • To minimize changes caused by inbreeding and genetic drift, the population should be maintained in such numbers as to give less than 1% inbreeding per generation.
  • 29. Rattus • Rattus contains 66 species • Rattus norvegicus or brown Norway rat • Rattus rattus or black rat • The two species differ considerably in their habitats, behavior and ecology. • Wild Rattus norvegicus has agouti -coloured fur- - has agouti gene which produces hairs with colour bands varying between brown –black and red – yellow. • Rattus rattus may have a more variable coat colour, but is mainly dark brown or black. • R. norvegicus lives mainly in burrow systems at ground level, whereas R. rattus tend to occupy higher areas in trees and roofs.
  • 30. History of the Norway Rat (R. norvegicus) • The first laboratory rats: • Albino rats (actually spontaneous mutation was seen) were brought into laboratories for physiological studies as early as 1828. • First breeding experiments in the 1870s and 1880s • White rats of European origin were brought to America shortly after this and became the foundation stock of American laboratory rats • The oldest strain of inbred rats dates from 1856. • The oldest purpose-bred strain of inbred rats, the PA strain, had been created by Helen Dean King at the Wistar institute in Philadelphia by 1909 . • The Wistar rat, and to a lesser extent, the Sprague- Dawley rat, gradually became the most popular rat strains for laboratory research.
  • 31. Laboratory rat • A laboratory rat is a rat of the species Rattus norvegicus which is bred and kept for scientific research. • Laboratory rats have served as an important animal model for research in psychology, medicine, and other fields.
  • 32. Comparison and contrast between • RAT : Wistar and Sprague Dawley Strains • Common name : Rat • Scientific name : Rattus norvegicus • Strain : Wistar and Sprague Dawley • Source: Denmark • Coat color: Albino
  • 33. Comparison and contrast between • Wistar rats → wider head, long ears, and the tail length always shorter than that of the body length. • Sprague - Dawley rats→ longer and narrower in head , longer tail, which may equal or be longer than the body length. • Wistar rats are more active than Sprague Dawley rats
  • 34. Strains of lab. rats • Albino Wistar : • Developed at the Wistar Institute in 1906. • Easy to handle and male aggressive behavior develops relatively late. • An outbred or random - bred strain and a large number of varieties exist worldwide.
  • 35. Strains of lab. rats • Albino Sprague - Dawley :  Originated by R. Dawley, Sprague-Dawley Company, Madison, Wisconsin, in 1925.  Now purchased by Harlan Sprague Dawley  Originally female albino Wistar rats were crossed with hybrid hooded males from an unknown origin. and subsequently to his white female offspring for seven successive generations.  Multiple lines, developed by inbreeding,  thereafter were outbred to develop a stable, heterogeneous stock.  Calmness and ease of handling
  • 38. Strains of lab. rat • Long - Evans hooded: • Developed by Dr. Long & Evans at Berkeley, California in 1910. • Crossing several Wistar females with wild gray male. • Head and extremities - black or brown • Rest of the body - white with pigmented eyes • easily handled • Level of aggressive behavior is generally high. • Behavioral and obesity research
  • 41. Uncommon strains or substrains • Apart from the traditional inbred and outbred strains, a wide variety of genetic selection lines are available. These lines are genetically selected for the presence or absence of certain behavioural or physiological characteristics. • E. g Roman High Avoidance (RHA) and Roman Low Avoidance (RLA) lines are selected for their behavioral performance in an active shock avoidance paradigm, using the Roman Wistar as the parental population. • The Kyoto Wistar was used to select the Spontaneous Hypertensive Rat (SHR) line, using high sympathetic reactivity as a selection criterion. • Most of these genetic selection lines are not commercially available • Can only be obtained via the specific research institutes that breed and select these lines.
  • 42. Shaking rat Kawasaki • Neurological mutant rat in the Wistar strain first described in 1988: • Neurological signs : shaking of the body and an ataxic-paretic gait from day 10 postnatal. • CNS: cerebellum: small, frequently vermis and paraflocculus lacking, malposition of the neurons in the cerebral cortex, hippocampus and cerebellum. • Abnormal myelinated fibers in the molecular layer of the cerebral cortex and in the central gray matter of the spinal cord. • Survival : The affected rats survive for about 1 month. • Genes : short deletion in the RELN gene; Reelin, product of RELN gene is essential for proper cortex lamination and cerebellum development. • good animal model of human congenital malformations with neuronal migration disorders.
  • 43. RCS rats • The Royal College of Surgeons (RCS) rat • The first known animal with inherited retinal degeneration. • Mutation in the gene Mertk results in defective retinal pigment epithelium
  • 44. Hairless rats • compromised immune systems and genetic kidney diseases • Over 25 genes that cause recessive hairlessness in laboratory rats • Common : rnu (Rowett nude), fz (fuzzy) and shn (shorn). • Rowett nudes, first identified in 1953 in Scotland, have no thymus. • severely compromises their immune system, infections of the RT and eye increasing the most dramatically. • Fuzzy rats (fz/fz rats) were identified in 1976 in a Pennsylvanian lab. • progressive kidney failure that begins around the age of one month causes death. • Shorn rats were bred from Sprague Dawley rats in Connecticut in 1998. • They also suffer from severe kidney problems.
  • 46. Fuzzy rats • fuzzy mutation has been mapped to a location on Chromosome 1 Homozygous infant rats have curly or twisted whiskers at birth. First coat is short, rough, and the hairs are broken, which gives the coat a wavy appearance. • This short coat may last through one or two hair cycles, but by 2 months of age most mutant rats have only sparse hair and a fuzzy appearance, or no hair at all. • By six months, all homozygous rats are usually smooth-skinned and remain so thereafter. • suffers from chronic, progressive nephrosis, or nephropathy, which shortened their lifespan to 16.6 months in males and 20.4 months in females. • Males averaged 16.6 months (range: 12-20 months), and females averaged 20.4 months (range: 17-26 months) at time of death. • decreased lifespan as compare to normal rats
  • 47. Shorn rats • The shorn locus has been mapped to a narrow area of Chromosome 7 • Shorn, a recessive mutation causing hairlessness, was discovered in 1993. • Shorn rats display a very sparse, patchy coat throughout their lifetimes. • develop abnormal hearts and kidneys which are yellow and bumpy instead of red and smooth. • tend to be smaller than normal rats and they die prematurely, at around 12-14 months of age
  • 48. Orthologues between rat and mouse genes causing hairlessness Rats Mice fuzzy (fz), Charles River hairless (hr) frizzy (fr) Rowlett Nude (rnu), New Zealand Nude (nznu) nude (Whn) shorn (shn) -- none -- -- none -- fuzzy (fz) -- none -- hairless (hr)
  • 49. Biobreeding Rat (BB) • Known as BB or BBDP rat is an inbred laboratory rat strain that spontaneously develops autoimmune Type 1 Diabetes. • BB rats are used as an animal model for Type 1 diabetes. The strain re-capitulates many of the features of human type 1 diabetes, and has contributed greatly to the research of T1D pathogenesis. • Two genes have been identified - the MHC Class II gene and Gimap5, causing a severe T cell lymphopenia. • Recently, 8 further loci on rat chromosomes 1,2,3,6 (2 loci), 12 and 14 have been shown to be linked to Type 1 Diabetes in the BB rat. • Non-obese diabetic or NOD mice, like the Biobreeding rat, are used as an animal model for type 1 diabetes. NOD mice exhibit a susceptibility to spontaneous development of autoimmune insulin dependent diabetes mellitus...
  • 50. Why rats can’t vomit ? • Rats have a powerful and effective gastroesophageal barrier (1) Rats can't relax the crural sling while contracting the rest of the diaphragm. – The diaphragm has two muscles: the crural (muscle fibers attached to the vertebrae, called the crural sling) and the costal (muscle fibers attached to the rib cage). For vomiting costal muscle contraction and crural muscle relaxation required. Doesn’t occur in rat. (2) they can't wrench open the esophageal sphincter. – esophageal sphincter is opened during vomiting with the help of the longitudinal muscle of the esophagus. Weak in rat. (3) rats lack the necessary neural connections to coordinate the muscles involved in vomiting. – Brainstem nuclei and the muscle systems used in vomiting, rats don’t have complex connections between the nuclei or between the brainstem and the viscera that are required for such a coordinated behavior. E. g Rat, mouse, guinea pig, rabbit
  • 51. Alternative to vomiting • Rats do experience nausea and have evolved an alternative to vomiting: • pica, the consumption of non-nutritive substances • When rats feel nauseous they eat things like clay, kaolin, dirt and even hardwood bedding (eating clay and dirt is a type of pica called geophagia). • Clay -- binds and inactivates chemicals so deactivates toxins. • Food avoidance Response- First line defence • Pica -- second line of defense against toxins.
  • 52. kangaroo rats • Norway rats, kangaroo rats, and cotton rats all look like "rats" to the casual eye, even though they have many other subtle differences that indicate they are not as closely related as they look. • Their resemblance to each other is actually only superficial -- they're all rodents with long tails, • Kangaroo rats are only distantly related to Norway rats. • They are both rodent species (they belong to the order Rodentia) • Kangaroo rats belong to the family Heteromyidae, while Norway rats belong to a different family called Muridae. • In fact, Norway rats are more closely related to house mice than they are to kangaroo rats, as both rats and mice belong to the same family Muridae.
  • 53. • Kingdom: Animalia • Phylum: Chordata • Class: Mammalia • Order: Rodentia • Family: Heteromyidae • Subfamily: Dipodomyinae • Genus: Dipodomys Kangaroo Rat
  • 55. Characteristics of Kangaroo rat • 19 species • Size : 10 to 20 cm, with a tail of equal or slightly greater length • Weight : 35 to 180 grams • Most distinctive features: very long hind legs & efficient kidneys. • Longer loop of Henle in the nephrons which permit a greater magnitude of countercurrent multiplication , can produce urine up to an osmolarity of almost 6,000 mosm/liter, which is five times more concentrated than maximally concentrated human urine at 1,200 mosm/liter. • Because of this tremendous concentration ability, kangaroo rats never have to drink; the water produced metabolically within their cells during oxidation of foodstuff (food plus O2 yields CO2 + H2O + energy) is sufficient for their body. • Don’t lose water by perspiring because have no sweat glands. • Can recover 90% of the loss by using metabolic water gaining the remaining 10% from the small amount of water in their diet.
  • 57. Cotton Rat • Cotton Rat Origin • In 1996, Harlan obtained a cotton rat breeding nucleus from National Institutes of Health, Bethesda, Maryland, and Virion Systems, Inc. • Any member of the rodent having genus Sigmodon. • build their nests out of cotton, and can damage cotton crops. • small ears and dark coats • North and South America • primarily herbivores
  • 58. • Cotton rats are a little more closely related to Norway rats. • They belong to the same family Muridae, but cotton rats are in a different genus, called Sigmodon, while Norway rats are in the genus Rattus. • Molars of cotton rats are S-shaped when viewed from above (genus- meaning S- tooth). • Sigmodon hispidus was the first model organism to be used in polio research. Cotton Rat
  • 59. Biological Classification • Kingdom: Animalia • Phylum: Chordata • Class: Mammalia • Order: Rodentia • Family: Cricetidae • Subfamily: Sigmodontinae • Tribe: Sigmodontini Wagner, 1843 • Genus: Sigmodon
  • 61. Cotton Rat Characteristics • Coat: color combination varies; gray, brown, black • Litter average: 5.5 • New World rodent: Sigmodon hispidus • Susceptible to a wide range of human infectious disease agents
  • 62. Cotton rats as model of infectious diseases Adenoviral vector-based gene therapy Infectious disease pathogenesis • Respiratory Syncytial Virus • Herpes Simplex (Type 1 & Type 2) • Parainfluenza Type 3 • Polio • Measles • Monkeypox • Metapneumovirus • Human Immunodeficiency Virus • Influenza Virus
  • 63. Cotton rats as model of infectious diseases Bacterial infections – Mycobyterium tuberculosis bovis – Haemophilus influenzae – Rickettsial infections – Staphylococcus aureus Fungal infections Parasitic infections
  • 64. Hamster • Kingdom: Animalia • Phylum: Chordata • Subphylum: Vertebrata • Class: Mammalia • Order: Rodentia • Suborder: Myomorpha • Superfamily: Muroidea • Family: Cricetidae • Subfamily: Cricetinae • Genera: Mesocricetus, Phodopus, Cricetus, Cricetulus, Allocricetulus, Cansumys, Tscherskia • 25 species
  • 65. Hamsters • Stout - bodied, stubby – tailed, virtually tailless, broad - headed, velvet-furred , cheek - pouched, burrowing and nest building rodents. • Origin: Middle East and Southeastern Europe • Commonly used: • Syrian hamster ( Mesocricetus auratus ), known also as Golden Hamster • Less often used: • Chinese (Cricetus griseus ) • European hamsters (Cricetus cricetus ) • Djungarian hamster (Phodopus sungorus), also known as the Winter white Russian dwarf hamster, Dzungarian dwarf hamster, Russian dwarf hamsters, Siberian hamster, Winter white hamsters, and Sapphire winter white Russian dwarf hamster
  • 66. Hamsters characteristics • Color and hair-type: cinnamon, cream, white, and "teddy bear" (the long-haired variety). • Unique anatomic feature of hamster: • 1. cheek pouches =pouching of the oral (mouth) cavity on both sides, extending alongside the head and neck to the shoulders. • Use : to store food and allow the hamster to transport food from where it is gathered to the hamster's den or nest. The food is then eaten later, at the hamster's leisure. • Represents false appearnace of tumors or abscesses. • 2. paired glands in the skin over the flanks: • Appear as dark spots within the haircoat and are much more obvious in males than females. • Glands are used to mark a hamster's territory and also have a role in sexual behavior.
  • 70. Golden Hamster • Unusual and unique features which make them particularly useful for certain experimental studies. • Immuno – genetic characteristics : marked tolerance to homologous, heterologous and human tumours, parasites, viruses and bacteria. • Reversible cheek pouches: allow tumour grafts from other species, including man, to grow freely and symmetrically without the need to induce immunosuppression. • Dental research: form and occlusion of their molar teeth closely resemble those of humans and the induction of lesions is possible without fracturing of the teeth, as in rats. • Teratology: short gestation period is advantageous • Thermophysiology and circadian rhythm studies • Use of Syrian hamster oocyte in assessing human spermatozoal fertilising potential. Quantifying the effects of various factors affecting human sperm function in vivo.
  • 74. Laboratory mouse • most widely used vertebrate species in biomedical research • Adv: – short reproductive cycle, – Short lifespan, – small size – low cost of maintenance • cancer and drug research, vaccine and monoclonal antibody preparation and evaluation of the safety and effectiveness of pharmaceutical products.
  • 75. Inbred mice • Immunology • Oncology • Microbiology • Biochemistry • Pharmacology • Physiology • Anatomy • Radiobiology • offer a high degree of genetic uniformity
  • 76. Dog • Kingdom: Animalia • Phylum: Chordata • Class: Mammalia • Order: Carnivora • Family: Canidae • Genus: Canis • Species: C. lupus • Subspecies: C. l. familiaris and C. l. dingo
  • 82. Use of dog • dog genome is similar in size to the genomes of humans and other mammals, containing an estimated 2.8 billion DNA base pairs. • excellent model for researching numerous diseases requiring subtle phenotyping • many breeds of dogs are prone to genetic diseases including cancer and autoimmune disorders that are difficult to study in humans
  • 83. Ferrets • Kingdom: Animalia • Phylum: Chordata • Class: Mammalia • Order: Carnivora • Family: Mustelidae • Genus: Mustela • Species: M. putorius • Subspecies: M. p. furo
  • 85. Dentition • 4 types of teeth (the number includes maxillary (upper) and mandibular (lower) teeth) • 12 small teeth incisors (only a couple of mm) located between the canines in the front of the mouth. used for grooming. • 4 canines used for killing prey. • 12 premolar—located at the sides of the mouth, directly behind the canines. The ferret uses these teeth to cut through flesh, using them in a scissors action to cut the meat into digestible chunks and to chew food • 6 molars (two on top and four on the bottom) at the far back of the mouth are used to crush food.
  • 87. Uses of ferrets • Share many anatomical and physiological features with humans • virology, reproductive physiology, anatomy, endocrinology, and neuroscience • Experimental animal model for human influenza • Used to study the 2009 H1N1 (swine flu) virus • Smith, Andrews, Laidlaw (1933) inoculated ferrets intra-nasally with human naso-pharyngeal washes, which produced a form of influenza that spread to other cage mates. • pathogenesis and treatment in a variety of human disease e. g cardiovascular disease, nutrition • Respiratory diseases such as SARS and human influenza, airway physiology, cystic fibrosis and gastrointestinal disease.
  • 88. • Study all aspects of canine distemper, a serious and fatal disease of dogs and many forms of wildlife. • Behavioral research: suited to certain studies regarding learned behaviors. • Neuroendocrinology studies : domesticated species whose estrous cycle in the female is easily monitored so an important animal model for reproduction research • Alternative to the use of dogs and non- human primates in toxicology studies. Uses of ferrets
  • 89. Mongolian gerbil • Kingdom: Animalia • Phylum: Chordata • Class: Mammalia • Order: Rodentia • Family: Muridae • Subfamily: Gerbillinae • Genus: Meriones • Subgenus: Pallasiomys • Biological name: Meriones unguiculatus
  • 90. Mongolian gerbil • known as the jird, clawed jird, sand rat, or desert rat. • Native to China and Mongolia • Introduced into the US in 1954. • The most common color is the agouti, shown here: light buff to white ventrum, with mixed white, yellow and black hairs dorsally, giving an overall brown fur color.
  • 95. Behavior • usually nonaggressive, curious and social. • If a gerbil escapes, it does not attempt to hide as other rodents do and will often return to its cage. • Nocturnal: most active in the evening with cycles of activity during the day. • Gerbils may form stable, monogamous pairs and the male may assist the female in rearing young. • When they are excited or agitated they may audibly stomp their large hindlimbs.
  • 96. Uses of Mongolian gerbil • Avg life : 3-4 years • Good capacity for temperature regulation • High incidence of spontaneous neoplasms with increasing frequency in aging animals (≥ 2 year). So unsuitable for chronic toxicity studies. • Malignancies involving the ovaries, ventral sebaceous glands, kidney, adrenal glands and skin. • Abdominal sebaceous gland pad in the gerbil is androgen dependent and readily observable
  • 97. Uses • Radiation studies: because they can tolerate much greater whole-body radiation exposure than other animal species. • Endocrine gland metabolism studies: one of the largest ratios of adrenal weight to body weight of all animals. • Experimental atherosclerosis • Valuable animal model for stroke research. Most animal species have a major arterial vascular supply to the base of the brain - the Circle of Willis. This circle is incomplete in the gerbil. Unilateral carotid ligation in the gerbil results in ipsilateral cerebral ischemia. • High incidence of spontaneous epileptiform seizures, usually precipitated by a novel environment. • Parasitology research- successfully infected with parasites common to other species
  • 98. Uses of Gerbil • Lipid metabolism: display lipemia and hypercholesterolemia even on rodent diets with standard fat composition. this results in hepatic lipidosis and gallstones, but not in atherosclerosis. • Reproduction studies to evaluate antifertility drugs • Auditory research: hearing curve is closer to man's than most common laboratory animals. • Psychology studies: due to exploratory and territorial marking behaviors • Toxicology research: studies of food additives, pesticides, industrial solvents and heavy metals. • Infectious disease research:
  • 99. • Kingdom: Animalia • Phylum: Chordata • lass: Mammalia • Order: Lagomorpha • Family: Leporidae • Genus: Oryctolagus Lilljeborg, 1873 • Species: O. cuniculus Rabbits
  • 100. Rabbits • small mammals • 8 different genera in the family classified as rabbits, including • European rabbit (Oryctolagus cuniculus), • Cottontail rabbits (genus Sylvilagus; 13 species), • Amami rabbit (Pentalagus furnessi, an endangered species on Amami Ōshima, Japan). • There are many other species of rabbit, and these, along with pikas and hares, make up the order Lagomorpha. • two living families, the Leporidae (hares and rabbits), and the Ochotonidae (pikas). • The male -- buck • The female – doe • young rabbit is a kitten or kit
  • 101. Rabbits • Use is declined over the last decade because of gradual and slight decline of the use of polyclonal antibodies produced in rabbits • Polyclonal antibodies still required bec’ they are quicker and easier to produce than the monoclonal antibodies • Pyrogen testing of intravenous fluids and other technical products intended for patients even though other test methods without live animals are being evaluated • Development of bio implant products such as dental implants and devices for orthopaedic surgery • Study of atherosclerosis after being given high - fat and high - cholesterol diets, which lead to the development of atherosclerotic lesions in the major arteries after approximately 2 months.
  • 102. Rabbits • WHHL (Watanabe heritable hyperlipidaemic): Spontaneously mutated strain develop atherosclerotic lesions in their blood vessels even without the high - fat diet • Toxicology: detection of teratogenic effects of drugs because the embryological development of the rabbit foetus is well known, the gestation period is short and rabbits produce a fairly large number of offspring • Experimental teratology • Cardiac surgery and disease, joint surgery, ophthalmology and studies of hypertension
  • 103. Opossum • Kingdom: Animalia • Phylum: Chordata • Class: Mammalia • Order: Didelphimorphia • Family: Didelphidae • Subfamily: Didelphinae • Genus: Monodelphis • Species: M. domestica
  • 104. Order: Didelphimorphia • small to medium-sized marsupials, with the largest just exceeding the size of a large house cat, and the smallest the size of a small mouse. • semi-arboreal (often inhabiting and frequenting trees but not completely arboreal =in burrows) • omnivores (eat everything), although there are many exceptions. • Most members of this taxon have long snouts (projecting nose, jaws, or anterior facial part of an animal's head.), • a narrow braincase, • Prominent sagittal crest (ridge of bone running lengthwise along the midline of the top of the skull (at the sagittal suture) of many mammalian and reptilian skulls). • dental formula is : 5.1.3.4: 4.1.3.4 • By mammalian standards, this is a very full jaw. The incisors are very small, the canines large, and the molars are tricuspid.
  • 105. Opossum • Gray short-tailed opossum (Monodelphis domestica) • Small member of the Didelphidae family • Possum = white dog • The first marsupial to have its genome sequenced. • Marsupiam: fold of skin, supported by epipubic bones, containing the mammary glands into which young ones are placed. • Habitat: Bolivia , Brazil and Paraguay • Frequently found in the exotic pet trade • Biomedical research • Also known as the Brazilian opossum, rainforest opossum and in a research setting the laboratory opossum.
  • 107. Opossum • Readily available animals • Suited for use in studies of – Melanoma – Hypercholesterolemia – Development of arteriosclerosis, angiogenesis and corneal cancer because they are altricial, – Developmental studies are also done on their extremely immature young. – An increasing number of researchers are using the laboratory opossum and considerable baseline data are now available. – M. domestica are easily cared for in standard rodent cages and can be fed standard pelleted fox laboratory diet.
  • 108. Primates • Primates: • Primates should only be used in research programmes where there is particular need in justified research programmes and where it can be demonstrated that the benefits to society outweigh the harms inflicted on the animals that are used.
  • 109. Cat (Felis catus) • Kingdom: Animalia • Phylum: Chordata • Class: Mammalia • Order: Carnivora • Family: Felidae • Genus: Felis • Species: F. catus
  • 110. Primates • The total number of primates used in research worldwide is estimated at between 100 000 and 200 000, with 64.7% involving Old World monkeys • Most (up to 70 %) are used in regulatory toxicology. • The most common research areas for which primates are used are: – infectious diseases (including HIV/AIDS) 26% – neuroscience 19 % – biochemistry 12 % – pharmacology/physiology 11 %
  • 111. New and old World monkeys • New World monkeys • E. g Squirrel monkey, marmoset • Native to Central and South America belong to family : Callitrichidae, Cebidae, Aotidae, Pitheciidae, and Atelidae • Old World monkeys • E. g Rhesus monkey • Native to Africa and Asia belong to family : Cercopithecidae
  • 112. Rhesus monkey • Rhesus Macaque (Macaca mulatta), also called the Rhesus Monkey • One of the best known species of Old World monkeys. • Kingdom: Animalia • Phylum: Chordata • Class: Mammalia • Order: Primates • Family: Cercopithecidae • Genus: Macaca • Species: M. mulatta
  • 115. Squirrel monkey • Squirrel monkeys and marmosets share many physical characteristics, including small size and ease of handling that contribute to their desirability as research subjects. • Squirrel monkeys ( Saimiri spp.) -- most commonly used neotropical primates in US. • Europe – marmoset is used • Adv: • The mean body weight of adult squirrel monkeys is less than 1 kg compared with female rhesus monkeys, which usually weigh 4 – 5 kg. • Smaller doses necessary sp. Expensive medications • easily adapt to laboratory housing
  • 117. Advs. of squirrel monkey • smaller spaces and less expensive cages req’ than larger primates, such as macaques and baboons. • Less risk of serious zoonotic disease transmission with squirrel monkeys and other neotropical primates than with macaques and other Old World primates. • Accidental exposures from bites and scratches can be managed in a manner similar to those from dogs and cats, and personal protective equipment required for handling squirrel monkeys is less extensive. • Reduced risk to laboratory workers combined with ease of handling, allow more procedures to be carried out without chemical restraint or expensive handling equipment. • Easily habituated to handling, which further reduces stress from manipulation. • Experimental procedures that must be performed without sedation can be carried out relatively easily in squirrel monkeys.
  • 118. Research models of squirrel monkey • Physiological studies of the effects of space flight -- ability to tolerate high gravitational forces • Atherosclerosis research- – Wild squirrel monkeys also have naturally occurring atherosclerotic lesions; fatty streaks and plaques in aortas resembling human atherosclerosis in lab. monkeys • Experimental induction of cholelithiasis • Reproductive biology
  • 119. Research models of squirrel monkey • malaria vaccine development studies- important animal model • Plasmodium spp. are host specific; therefore the animals used for studies of human malaria must be susceptible to the same strains of Plasmodium that cause disease in humans. • The Bolivian squirrel monkey are superior model than the Guyanese squirrel monkeys (S. sciureus sciureus) P. Falciparum
  • 120. • One of the most susceptible non -human primate species to experimental infection with Creutzfeldt - Jakob disease (CJD) • Transmissible spongiform encephalopathies Research models of squirrel monkey
  • 121. Transgenic animals • Genetically engineered or modifi ed mice are those with induced mutations, including mice with transgenes, with targeted mutations (knockouts) and with retroviral, proviral or chemically induced mutations . • Transgenic technology focuses on the introduction or exclusion (knockouts) of functional genetic material in the germ line of an animal, thus changing the genetic characteristics of an organism and its progeny.
  • 122. • The most frequently used methods for genetic transformation of the germ line are microinjection of DNA into the pro nucleus of fertilized oocytes and the injection of transfected embryonic stem (ES) cells into normal mouse blastocysts, resulting in a subsequent generation of chimeras. • These techniques have led to the rapid development of a variety of animal models, designed for the study of gene regulation, gene expression, pathogenesis and the treatment of human and animal diseases (eg, Alzheimer ’ s disease, growth hormone disturbances, poliovirus vaccine testing ). Transgenic animals