Rodent Biology, Comparation between rats and humans

1. 1
Rodent Biology
Pradeep Singh
prdnarwat@gmail.com

2. 2
Contents
• Taxonomic classification
• Introduction
• History
• Difference between mouse and rats
• Difference between laboratory rats and wild rats
• Comparison of rat and human ages
• Common inbred and outbred strains
• Sexing, Reproduction and Pups development
• Comparative anatomy of rats and humans

3. 3
General Features
Rat Human
Class Mammalia Mammalia
Order Rodentia Primata
Family Muridae Hominidae
Genus and Species Rattus norvegicus Homo sapiens
Chromosome
number (2n)
42 46
Sexual maturity 4-7 weeks 10-15 years
Life span 2.5 – 3.0 years ~ 70 years
Gestation period 21-24 days ~ 40 weeks
Mammary glands 12 (6 pairs) 2 discrete, pectoral
Male nipples Absent Present

4. 44
Taxonomic Classification
Kingdom : Animalia
Phylum : Chordata
Class : Mammalia
Order : Rodentia
Family : Muridae
Genus : Rattus
Species : norvegicus

5. 55
Introduction
• Found worldwide except Antarctica
• Binomial Nomenclature : Rattus norvegicus (Berkenhout, 1769)
• Common Names : Brown Rat, Sewer Rat, Norway Rat, Wharf Rat, Common Rat,
Hanover Rat, Norwegian Rat, etc.
• R. norvegicus was one of the first mammalian species domesticated for scientific
purposes.
• Replaced the less aggressive R. rattus in most parts of the world except warmer areas.

6. 66
History
• Rattus norvegicus (2N=42): thought to have originated in temperate Asia. It expanded
into Europe in the 8th Century and eventually into the Americas in the late 1700’s. By
now it spread worldwide. The name of “Norway rat” has no particular geographic
significance, although they are believed to have migrated to Western Europe via the
Norwegian Peninsula
• Rattus rattus (2N=38): spread from Southeast Asia into Europe around the 12th Century,
reaching the Americas in the 16th Century. Largely responsible for the spread of Bubonic
plague (“Black death”) to Europe in the 14th century (it killed about a quarter of the
European population).

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Use in Laboratory (since mid 1800s)
• Philipeaux studied adrenalectomized white rats in France in 1856 with published
reports of nutritional and breeding research.
• Neuroanatomical studies by Henry Donaldson at the University of Chicago in the early
1890’s represented the first known experimental use of rats in the USA. He later
established Wistar Institute in Philadelphia that will have a major role in the
development of the rat as an important laboratory animal similar to the impact the
Jackson laboratory had on the development of the laboratory mouse.
• The Wistar bloodline has contributed more strains of rats than any other line.

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Mouse
• Smaller (12-20 cms)
• Triangular snout with long whiskers
• Produce 40-100 droppings/day
• Long, thin, hairless tail
Rat
• Larger (about 40 cms)
• More blunt snout
• Produce 20-50 droppings/day
• Thick tail, usually hairless and scaly

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Difference between Laboratory Rats and
Wild Rats
• Lab rats have smaller adrenal glands, especially the cortex.
• Ovaries, testes, and secondary sex glands are the same size but mature earlier and
function continuously (no seasonal cycle) in lab rats.
• Better fecundity.
• Shorter life span (2-3 years for lab rat compared to 4-5 years for wild rats).
• Laboratory rats overall have smaller body size.

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Behaviour
• Nocturnal animals with most activity occurring during night time and early morning
• Typically non-aggressive, inquisitive and easily trainable
• Frequent handlings encourage their non-aggressive nature as they adapt to new
environments or experimental situations
• Improper handling, nutritional deficiencies can evoke fear responses
• Feel most comfortable in small, dark, confined spaces
• Coprophagic behaviour - Important for obtaining Vitamin B produced by bacterial
action in the colon
• In general, males are less likely to fight when housed together than are male mice. Post
parturient females may fight amongst themselves.

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Comparison of Rat and Human Ages

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Correlation of days or years of rat age with humans

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Common Inbred Strains

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Common Outbred Strains

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Sexing
• Sexing of rodents is based upon ano-genital distance
• Males have a greater distance between the anus and urogenital opening than
females.
• An opposite sex comparison is advisable initially.
http://neurocndm.mcgill.ca/uploads/file/Handout%2
0Rat%20Module%201.pdfhttp://diakonoi.org/sexing-baby-rats/

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Reproduction
S.No. Reproduction Rats Humans
1. Puberty 6-8 weeks Girls- 11
Boys- 12
2. Estrous cycle 4-5 days 28 days
3. Gestation 21-23 days 280 days
4. Size of litter 8-14 pups Not present
5. Birth weight 5-6 gm 3.5 kg
http://ratguide.com/health/basics/vital_statistics_in_rats.php

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Carnegie Stage 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Human Days 1 2-3 4-5 5-6 7-12
13-
15
15-
17
17-
19
20 22 24 28 30 33 36 40 42 44 48 52 54 55 58
Mouse Days 1 2 3 E4.5 E5.0 E6.0 E7.0 E8.0 E9.0 E9.5 E10
E10.
5
E11
E11.
5
E12
E12.
5
E13
E13.
5
E14
E14.
5
E15
E15.
5
E16
Rat Days 1 3.5 4-5 5 6 7.5 8.5 9 10.5 11 11.5 12 12.5 13 13.5 14 14.5 15 15.5 16 16.5 17 17.5
Comparative rate of Early Embryo development

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Pups Development
The first four weeks of a rat’s life are filled with dramatic changes.
At birth the pup is naked, blind, and completely dependant upon its mother for
everything.
Week 1
No fur, only slight
whiskers and eyelids
sealed
By day 4, colors and
patterns start showing.
Ears starts to develop.
The babies get more active as the first week progresses. All of their needs at this age are supplied by the mother.
She feeds them, cleans them, stimulates them to urinate and have bowel movements, keeps them warm, and
protects them.
Fingers and toes are lengthening and
separating, and by the end of the first
week, facial features become more
prominent. Sex can be determined.
http://ratguide.com/breeding/baby_development/birth_to_weaning.php

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Week 2
Babies are covered with light fuzz,
starts to crawl, ears become
separated from the head. Pup rat
still cannot hear, although it can
sense vibrations.
Ear canal opens, allowing the them
to hear. They begin to emerge
from the nest and walk, although a
bit unsteadily at first. Mother is
still feeding the babies.
Some of the babies’ eyes have
started to open. But the vision is
blurred. Fur completely covers their
bodies, female pups develop nipples.
Week 3
At this age the babies are able to run. Babies are old
enough to drink without a nipple. As their appearances
become more distinctive so do their individual
personalities.

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Week 4
Wrestling and eating are the
two preferred activities. Mom
is nursing them less often.
The babies are now using the
water bottle, eating lab block
and seed mix, and joining
mom in eating snacks.
Babies often go through a
molt at about this time and
may have strange color or
texture “patterns” in the coat
as new hair comes in. Handle
the babies every day to
socialize and get them ready
for their new homes.
The babies are now weaned.
Their basic personalities are
pretty well established, and
each day they show increased
individuality.
Pup rats mature quickly. Remember to separate the males and the females by the time they are 5 weeks old to
prevent any pregnancies. You can leave the females in with their mother. The boys will need their own cage.

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Age in days Age in weeks/months Development stages
Birth
Hairless, toothless, closed eyes and
ears relies on smell of mother/siblings
4 days 4 Days Hair begins to appear
10 days 1.5 weeks Covered with hair
13 days Almost 2 weeks Eyes and ears open
40-50 days 5 weeks to 7 weeks
Weaned at 5 to 6 weeks
Sexual maturity
72 days 2.5 months Young adult
250-300 days 8 – 10 months Young adult
1000-1300 days
32 – 42 months (2.7 to 3.5
years) end of normal
lifespan
Full grown; males larger than females
http://diakonoi.org/sexing-baby-rats/

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Vital Statistics
S. No. Vital statistics Rats Humans
1. Temperature 37.7°C (99.85°F) 36.5–37.5 °C
(97.7–99.5 °F)
2. Respiratory rate/minute 71 - 146 12-16
3. Heart rate/minute 250-493 60-100
4. Weight (average adult) Male – 250-550 gm
Female- 225- 400 gm
57.7 kg (Asia
average)
5. Life span (average)
24-40 months 79 years
http://ratguide.com/health/basics/vital_statistics_in_rats.php

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VISION
• The animal's perception of its surrounding world is called its ümvelt.
• Rats probably perceive just a hint of ultraviolet, blues and greens. Somewhat like humans with red-
insensitive color blindness, Retinas have mainly rods and only few cones.
• Albino rats have unpigmented irises that do not block light well, so their retinas are constantly dazzled
with light, leading to retinal degeneration. Hence, the visual acuity of albinos is much worse than
normally pigmented rats, around 20/1200.
• Rats probably use their vision to detect large, moving, distant objects and to orient themselves in
space. At close range, rats rely on other senses: whisker touch and smell.
http://www.ratbehavior.org/RatVision.html
Human vision Normally-pigmented rats have blurry
dichromatic vision with a little color
Albino rats may see a very
blurry, light-dazzled world

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while the world may look blurry to the rat...
his whiskers will provide detailed information
about what he can touch as he moves through
the landscape.
SMELL AND HEARING
• Over 1% of his DNA is devoted to detecting odours.
• humans can hear up to 20 kHz, but rats can hear up to 90 kHz!

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• The rat's tail has a thermoregulatory function: it serves as a heat-loss organ.
• Has a large surface to volume ratio, and is perfused with many blood vessels, especially at the tail tip and
midlength.
THERMOREGULATION
http://www.ratbehavior.org/RatTails.html
Cross section of the base of a rat's tail at two different body temperatures (37º and 40º C). At 40º C,
the diameter of the blood vessels (especially the veins) is larger than at 37º C. This larger diameter
permits more blood to flow through the tail: 15% more blood flows through the arteries and 125%
more flows through the veins at 40º C than at 37º C. Adapted from Vanhoutte et al. 2002.

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FEEDING
• Rats are omnivorous, like humans.
• Lab blocks(contain all the essential vitamins, minerals,
amino acids, fatty acids and macronutrients) provide the
best nutrition for rats.
• Having fresh water at all times ensures the rat is not at risk for
dehydration.
• Signs that rat may be protein-deficient:
1. Chronic infections
2. Stress fractures in bones
3. Hair loss
http://ratguide.com/care/nutrition/diet.php

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COPROPHAGY
• Coprophagy is the eating of excrement and is a normal nutritional
behaviour for rats.
• Rats will regulate the amount of feces eaten according to their
nutritional needs.
• Thiamin and pantothenic acid deficiencies will cause a marked
increase in coprophagy.
• Preventing rats from eating their feces can lead to deficiencies of
vitamin K, complex B vitamins, and biotin and can cause other
vitamin deficiencies to develop.
• when not permitted to ingest their fresh feces show a stunted
growth rate.

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ENVIRONMENT
• Rats do need periods of total darkness or else they can experience health and even
reproductive problems.
• Temperature: 20-26 degrees Centigrade (68-78.8 Fahrenheit).
• Ambient temperature for breeding: 24-26 degrees Centigrade (75.2-78.8 degrees
Fahrenheit).
• Relative humidity: 30-70%
• Housing area: 40 inch² per 300 gm wt. of rat
• Proper bedding, hide away areas, toys, and accessories to provide a healthy and
stimulating environment for your rat.
• Cleanliness is a must for rat housing because Ammonia buildup can cause damage
to their delicate respiratory systems. http://ratguide.com/care/environment/

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Dose Conversion Calculations
• Larger animals have lower metabolic rates.
• Physiological process of larger animals is slower.
HED (mg / kg )=Animal NOAEL (mg / kg) × {Animal
Weight(kg)/human Weight(kg)}^1-0.67
0.67 account for difference in metabolic rate, to convert doses
between animals and humans.
• NOAEL: no observed adverse
effect levels.
• LEVEL: Refers to the dosage,
generally expressed as mg / kg
• HED: Human Equivalent dose

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EXAMPLE:
For a newly developed drug molecule, the NOAEL value in rat weighing approximately 150 g
is 18 mg/kg.
HED mg / kg = 18×( 0.15 / 60)^0.33 = 2.5 mg / kg
Thus, for a 60 kg human, the dose is 150 mg. This HED value is further divided by a factor
value of 10; thus, the initial dose in entry into man studies is 15 mg.
Body weight is not the lone factor which influences the scaling for dose calculation.
• Km= average body weight (kg) / BSA
• HED mg / kg = Animal dose (mg/kg) × (Animal Km / Human Km)
Nair, A., & Jacob, S. (2016). A simple practice guide for dose conversion between animals and human. Journal of Basic and
Clinical Pharmacy, 7(2), 27. doi:10.4103/0976-0105.177703

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EXAMPLE: Rat dose (50 mg/kg) by 6.2 or multiply by 0.162, the HED is 8.1 mg/kg.

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Comparative Anatomy

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Skeletal System

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Skeletal system Rat Human
Vertebrae C 7
T 13
L 6
S 4
C 27-31
C 7
T 12
L 5
S 5
C 4
Osteon (Haversian system) Absent Present
Epiphyseal growth plate Persist throughout life Persistent only during growth and
development
Bone marrow Persistent throughout in axial and
appendicular skeleton
Persistent only in long bones in
adults

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Nervous System
•
http://www.gensat.org/imagen
avigator.jsp?imageID=92969
https://www.researchgate.net/figure/1-An-illustration-of-
the-human-brain-with-several-regions-labeled-Source-
Heart-and_fig5_291346848

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Brain Rat Human
Lobes defined by external
landmarks
Absent Present
Sulci and Gyri Absent Present
Olfactory bulb Very large Small
Meninges Thin Thick, well developed
Basal ganglia Combined caudate nucleus
and putamen
Separate caudate nucleus
and putamen
Spinal Cord Rodent Human
Spinal formula C7 T13 L6 S4 Cd27-30 C7 T12 L5 S5 Cd4
Spinal Cord Terminates at the level of
the intervertebral disc
between L3 and L4
Terminates at the level of
the intervertebral disc
between L1 and L2
Sciatic nerve origin Rat: L4-L5 L4-S5
Lateral horn Less prominent More prominent

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Respiratory System

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Circulatory System

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Heart Rat Human
Heart shape Oval to spherical Conical
Heart weight 0.5-2.5 g 200-300 g
Heart rate 300-400 beats/min 60-100 beats/min
Cardiac output 70-80 ml/min 4.5-5.5L/min
Rests on diaphragm No Yes
Location of coronary
arteries
Intramyocardial Extramyocardial

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Lymphatic System

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• The lymph nodes of rodents are very small compared to
human lymph nodes; therefore, histological appearance
varies based on the plane of section in rodents more so
than for human nodes.
• Lymph nodes in young rodents do not have well developed germinal centers,
whereas germinal centers are seen in humans at all ages.
• Distribution of B- and T-cells within lymph nodes is the same in all three species
(mice, rat and humans).
• Spleen:
o Red pulp in the rodent is a site of normal hematopoiesis. In the adult human,
significant extramedullary hematopoiesis is not normal.
o The B-cell zone predominates in the rodent white pulp, whereas the T-cell zone
predominates in the human spleen.
• Tonsils are absent in rodents but present in humans.

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Digestive System
RAT
HUMAN

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Rat Liver Vs Human Liver
Comparative Anatomy and Histology: A mouse, Rat and Human Atlas, 2nd Edition

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Rat Human
Esophagus Well defined upper and lower
sphincter
Well defined upper sphincter
whereas lower sphincter is less well
defined
Stomach Forestomach: Present
Rugae folds: Present
Forestomach: Present
Rugae folds: Present
Small Intestine Length: ~170 cm Length: ~7000 cm
Large Intestine Functional cecum is present Cecum is present but not
functional

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Non-Alcoholic Fatty Liver Disease
• Nonalcoholic fatty liver disease (NAFLD) includes simple fatty infiltration (a benign condition called fatty liver),
whereas nonalcoholic steatohepatitis (NASH) is defined as the presence of fat leading to lipotoxicity and
inflammatory damage to hepatocytes. Histologically, NASH is indistinguishable from alcoholic hepatitis.
• Possible mechanisms for steatosis include reduced synthesis of very low density lipoprotein (VLDL) and increased
hepatic triglyceride synthesis (possibly due to decreased oxidation of fatty acids or increased free fatty acids being
delivered to the liver).
• Inflammation may result from lipid peroxidative damage to cell membranes. These changes can stimulate hepatic
stellate cells, resulting in fibrosis. If advanced, NASH can cause cirrhosis and portal hypertension.
• In response to chronic injury, bridging cords of collagen and nodular regeneration characteristic of cirrhosis are
readily apparent in the human liver and to a lesser extent in the rat, but rarely occur in the mouse despite
enthusiastic claims of “cirrhosis.”

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• Currently, there is no non-invasive biomarker available for the diagnosis of NAFLD and NASH. Rats serve as
important disease model to understand the pathophysiology of NAFLD/NASH.

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• Cirrhosis is a late stage of hepatic fibrosis that has resulted in
widespread distortion of normal hepatic architecture. Cirrhosis
is characterized by regenerative nodules surrounded by dense
fibrotic tissue.
• Symptoms may not develop for years and are often nonspecific
(eg, anorexia, fatigue, weight loss). Late manifestations include
portal hypertension, ascites, and, when decompensation occurs,
liver failure. Cirrhosis is usually considered irreversible.
• Rats plays an important model to study the pathophysiology of
cirrhosis which mainly include portal hypertension.
Cirrhosis

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Endocrine System

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Urinary System

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RAT
HUMAN
Female Reproductive System

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Male Reproductive System

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58. 5858
Routes of Drug Administration in Rats
Route Needle size Maximum Volume
Intra-muscular 22-30 G 0.3 mL
Subcutaneous 22-30 G 5 mL
Intradermal
(must be done under anaesthesia)
25-30 G 0.1 mL
Intraperitoneal
(Lower left/right quadrant of abdomen at 30˚ angle)
22-30 G 5 mL
Intravenous
(Injection site – Lateral vein)
25-30 G 0.5 mL
Oral gavage
(Length of the needle from the tip of the nose to the
first rib)

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