To describe the importance of laboratory animals in scientific researches.

1. Practical Experiments in
Laboratory Animals

2. food, transport ,companionship

3. • The use of animals in experimental research
parallels the development of medicine,
which had its roots in ancient Greece.
• Where Aristotle (Written 350 B.C.E).
• and Hippocrates investigated the structure
and function of the human body).

4. These works are based mainly on dissections of
animals,
since performing autopsies on humans was not
permitted at that time.

5. • Galen (130 AD to 201 AD), physician to the
Roman Emperor Marcus Aurelius,
• Conducted physiological experiments on
pigs, monkeys and dogs that provided a
basis for medical practices in the centuries thereafter.

6. • After Galen, experimental science stopped until the
beginning of the Renaissance,
• when Vesalius took up the empirical approach, starting
with anatomical studies.
• later, physiological studies were also carried out.

7. 1600's - Function of the lungs, Measurement of
blood pressure.
1700’s The development of Cartesian philosophy in the Century meant that
experiments on animals could be performed with little ethical concern.
1800's – Vaccination, Understanding of infectious
diseases.
1900's - Antibodies, hormones.
1930's - Mechanism of nerve impulses, tumor
viruses.
1940's - Embryonic development

8. 1960 - Monoclonal antibodies, liver functions
1970's - Transplantation antigens, brain
functions, Discovery of prostaglandins.
1980's - Development of transgenic animals.
1990's - Understanding auto-immune disorders,
In vitro fertilization, cloning

9. The use of laboratory animals
• Today, 75 to 100 million vertebrates are used per year worldwide in research,
teaching and testing for a wide range of purposes.
• Drug research.
• Testing of vaccines.
• Testing of biologicals.
• Cancer research.
• while the remaining 30% are used for
• purposes such as fundamental research.
• for diagnostic purposes.
• for teaching, etc.
account for about 70% of the animals used,

11. Why are laboratory animals used in clinical
research?

12. To advance scientific understanding
The basic cell processes are the same in all animals, and they perform similar
vital functions such as breathing, digestion, movement, sight, hearing and
reproduction.
Simple animals can be used to study complex biological systems such as the
nervous or immune systems, which follow the same basic organization and
function in all animals.

13. As models to study disease
Studying disease mechanisms in animal models leads directly to the development of new
technologies and medicines that benefit both humans and animals.
•While contributing to our understanding of diseases, animal models enable researchers to
explore potential therapies in ways which would be impossible in humans.
•Animals which are altered to create models of disease are known as induced models.
•These animal models help researchers understand what happens in the body following this
type of damage, and have been used in the development of new therapies.
•Recent advances in genetic technology have allowed the development of transgenic
animals, which have new genes inserted into their DNA, allowing them to develop human
diseases which do not naturally affect them.

14. To develop and test potential forms of treatment
Once researchers learn more about a particular disease, animals are used to develop and test
these potential therapies as part of the applied research process.
•Data from animal studies is essential before new therapeutic techniques and surgical
procedures can be tested on human patients.
•For example, medicines for Parkinson's disease have been developed using animal models
with induced Parkinson's-like symptoms.
•Diagnostic tools such as scanners, and implants such as pacemakers are safe and effective only
because they were developed and tested in animals.
•Many surgical techniques, such as open heart surgery and heart transplants, rely on methods
and equipment that were developed using animals.

15. To protect and ensure the safety of people, animals and the environment
New medicines require testing because researchers must measure both the beneficial
and the harmful effects of a compound on an organism.
•The animal tests provide data on efficacy and safety of a new compound.
They not only identify potential safety concerns, but also determine the doses which
will be given to volunteers and patients during the first human trials.
•Testing on animals also serves to protect consumers, workers and the environment
from the harmful effects of chemicals.

18. RODENT MAMMALS USED IN DRUG DEVELOPMENT

19. RAT (Rattus norvegicus)
Rats have been useful for research in the following fields-
• Study of analgesics and anticonvulsants.
•Study of oestrus cycle, mating behavior and lactation.
•Gastric acid secretion
•Hepatotoxicity studies
•Study on mast cells
•Bioassay of various hormones, such as insulin, oxytocin, vasopressin .
• Rats are better at removing toxins from their bodies than humans, so it may be possible to refine the use of
rats in toxicology studies.
•Rat brain tissue is extensively employed in radio-receptor ligand studies.

20. WISTAR RATS
These were developed at the Wistar Institute in 1906 and is notably the first rat developed to
serve as a model organism.
The Wistar rat is currently one of the most popular rats used for laboratory research.
It is characterized by its wide head, long ears, and having a tail length that is always less than
the body length.
SPRAGUE DAWLEY RATS
These rats typically have increased tail to body length ratio as compared to Wistar rats

23. Long-Evans rat
They are utilized as a multipurpose model organism,
frequently in behavioral and obesity research
ZUCKER RATS –
They are genetically modified rats used to study obesity and hypertension

24. BIOBREEDING RATS –
They are used as models to study autoimmune type 1 diabetes

25. HAIRLESS RATS –
They are use to study compromised immune systems and genetic kidney diseases.

26. MICE (Mus musculus)
•They are most widely used in clinical research as they are small, inexpensive and
easy to handle .
• Mice are used in a vast range of experiments, many of which are classified as
fundamental research, investigating the physiology of mammals.

27. They have similar reproductive and nervous systems to humans, and suffer from same
diseases such as cancer, diabetes and even anxiety.
•Their short life span and fast reproductive rate, makes it possible to investigate
biological processes at all stages of the life cycle.
• Swiss albino mice are the most commonly used species.

28. Mice
• Normal temperature:- 37.4
• Pulse rate:- 120
• Estrous cycle:- 4-5 days
• Gestation period:- 19-21 days
• Weaning age:- 19-21 days
• Mating age:- 6-8 weeks
• Litters:- 8-12 yearly; average litter, 7-8
• Room temp.:- 20-21
• Humidity:- 50-60 %
• Weight- weaning : 7g ,adult:- 25-28 g

29. EXPERIMENTAL USES
• Toxicological studies
• Teratogenicity studies
• Bioassay of insulin, screening of analgesic and anticonvulsant drugs
• Screening of chemotherapeutic agents
• Studies related to genetics and cancer research
• Drug action on CNS

30. GUINEA PIG(Cavia porcellus)
•Guinea pigs have biological similarities to humans, which make them useful in many fields
of research.
•Vitamin C was discovered through research on guinea pigs.
•Their serum contains enzyme Aspariginase which shows anti-leukaemic action.
They were also crucial to the development of :
•Vaccines for diphtheria, TB,etc
•Evaluation of local anaesthetics

31. • Guinea pig
• Rectal temp.:- 37.6-38.9
• Normal respiration rate:- 80 per minute
• Pulse rate:- 150 per minute
• Gestation period:- 59-72 days( avg. 63 days)
• Weaning age:- 14-21 days
• Mating age:- 12-30 weeks
• Litters:- 3 yearly ;average litter,3
• Room temp:- 18.5- 21
• Humidity:- 45%
• Weight –weaning :- 120g, adult:- 200-1000g

32. • Antibiotics, Histamine and antihistamines
•Anticoagulants
•Bronchodilators
•Bioassay of Digitalis.

33. Guinea pig tissue
•Guinea pig blood components and isolated organ preparations such as lung and intestines are
extensively used in research to develop new medicines.
•Terminal portion of ileum used for screening spasmodic and anti spasmodic agents.
•They were important in the discovery and early development of beta blockers to treat high
blood pressure and drugs to treat stomach ulcers.
•Numerous developments have used their intestine for example the anti-nausea drugs used by
cancer patients and the identification of naturally occurring pain killing substances known as
enkephalins.

34. Allergies and respiratory diseases
•The extreme allergic reaction, anaphylactic shock has been studied extensively in guinea
pigs.
• Their airway is sensitive to allergens, so it has been widely used in asthma studies.
The inhaled medications that are the mainstays of asthma treatment were developed using
guinea pigs as were orally-active drugs for asthma such as montelukast.
•They are also used in the testing of vaccines against anthrax and new medicines to treat
drug-resistant tuberculosis.
•Also used to test for allergic skin reactions due to their skin sensitivity.

36. Nutritional research
Along with Vitamin C , guinea pigs also need high levels of folic acid, thiamine, arginine and
potassium, which make them useful in nutrition studies.
They also carry most of their plasma cholesterol in low density lipoprotein, so they are also
useful in the study of cholesterol and lipoprotein metabolism.

37. HAMSTER(Mesocricetus Auratus)
•Third commonly used laboratory animal.
•Two species are commonly used-
 Golden or syrian hamster
 Chinese hamster

38. •Hamsters are used extensively in oncovirus, Influenza virus and Respiratory Syncytial Virus
(RSV) studies and vaccine production.
•Their cheek pouches do not have lymphatic drainage and hence they are ideal sites for tissue
transplants.

39. Syrian Hamster is most commonly used for biomedical research because of ease of
availability.
•European Hamster is more suitable model for highly concentrated and prolonged
smoke inhalation studies.
•Chinese Hamster is suitable for cytogenesis research.

40. PIGEON (Columbia livia)
•Pigeons are good screening models for anti-emetic
drugs.
•They also find application in bioassay of prolactin.
•Used for screening of intravenous anaesthetics.
•Used for standardization of cardiac glycosides.

41. Animal models of disease

42. Many examples of animal models predict with fair accuracy therapeutic efficacy in
humans
ex:-
ferret vomit when placed in swaying cages. (Antiemetic drugs).
Rats inject with irritant chemicals. (Anti-inflammatory drugs such as rheumatoid
arthritis).

43. Models for many important disorder such as
Based on knowledge of physiology of the condition.

44. Used successfully to produce
Even though their success in predicting therapeutic efficacy is far from perfect

45. Ideally , an animal model should resemble the human disease in the following
ways.
- Similar pathophysiological phenotype (face validity).

46. - Similar causation (construct validity).

47. - Similar response to treatment (predictive validity).

49. Face validity
In practice there are many difficulties.
Shortcomings of animal models are one of the main roadblock on the route from basic
medical science to improvement in therapy
Difficulties
- Psychiatric disease
(Defined by phenomena in human *** Impossible to observe in animals)
Out of face validity

50. Examples
mania
delusion
Migraine
attack
Depression
Autism
Anxiety

51. Construct validity
- The cause of many human disease is complex or unknown.
- To achieve construct validity for degenerative disease
- ( Alzheimer, Osteoarthritis, Parkinson Disease)
- Upstraem ( causative)
- Downstream ( symptomatic)

52. predictive validity
Relying on response as a test for predictive validity carries the risk that drug acting by novel
mechanism could be missed.

53. Example:- Schizophrenia
- Dopamine antagonists are effective
- many models used are designed to assess dopamine antagonist in the brain.

54. Genetic and transgenic animal models
Genetic approaches are increasingly used as
- An adjunct to conventional physiological and pharmacological approaches to disease
modelling
by selective breeding ---- pure animal strain ---- resembling human disease.

55. Examples:-
- Spontaneously hypertensive rats
- Obese mice
- Epilepsy prone dogs and mice
- Rats deficient with ADH secretion

56. Study the obesity **** type 2 DM
inactivation of the leptin gene

57. - High food intake
- Gross obesity
- Impaired blood
glucose regulation
- Vascular
complications
Good face
validity
Responding to
pharmacological
intervention similarly
to human
Good
predictive
validity
Obese human are
not leptin deficient
Poor
construct
validity

58. • Genetic manipulation of the germline to generate
transgenic animals.
• Is of growing importance as a means of replicating
human disease states in experimental animals
• Provide animal models that are expected to be more
predictive of therapeutic drug effects in human

59. Versatile Technology (1980)
inactivate
individual genes
mutate genes to
pathological form
overexpress genes
introduce new
human genes
allow gene
expression to be
controlled by the
experimenter

60. Ex:
mice overexpress mutated forms of the amyloid precursor protein or presenilins
which are important in the pathogenesis of Alzheimers
symptoms resemble for alzheimers

61. ex:-
Parkinson's disease over expression of synuclein ( protein characteristic of the disease)

62. ex:-
transgenic mice with mutations in tumor suppressor genes and oncogenes.
Widely used as models for human cancers.

63. Ex:-
mice with adenosine receptor inactivated ----- behavioral and cardiovascular
abnormalities such as
- Increased aggression.
- Reduced response to noxious stimuli
- Raised blood pressure.