animal models

ANIMAL MODAL

M. VharshiniDepartment of Biomedical Sciences

Sri Ramachandra University

PHARMACEUTICAL BIOTECHNOLOGY

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DEFINITION• Weggler in 1983 defined an animal model as a living organism with an

inherited, naturally acquired, or induced pathological process that in one or

more respects closely resembles the same phenomenon in men.

• The institute of laboratory animal resources(ILAR) of the National Academy

of Sciences adopted and modified Weggler’s definition as follows:

An animal model is a living organism in which normative biology or behavior can be

studied, or in which a spontaneous or induced pathological process can be investigated,

and in which the phenomenon in one or more respects resembles the same phenomenon in

humans or other species of animal.

PHARMACEUTICAL BIOTECHNOLOGY -ANIMAL MODELS

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MAJOR ADVANCES IN RESEARCHES THAT INVOLVED ANIMAL MODALS

1600's - Function of the lungs, Measurement of blood pressure.

1800's – Vaccination, Understanding of infectious diseases

1900's - Antibodies, hormones

1930's - Mechanism of nerve impulses, tumor viruses.

1940's - Embryonic development

1960's - 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


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ANIMALS USED IN RESEARCH


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RODENT ANIMAL MODEL:RatMiceGuinea pigs Hamster

NON – RODENT ANIMAL MODELS:

Rabbit MonkeyCatDog

TRANSGENIC ANIMALS

RODENT ANIMAL MODEL 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.


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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.

•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.


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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


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DIFFERENCE BETWEEN RATS AND MICE

•The rat is much larger in size and has greater body wieght as compared to the mouse.

•The mouse has a pointed face when compared to the rat.

•The rat has a thick and heavy tail. On the other hand, a mouse has a very thin tail

•The rat has a higher pair of chromosomes, ie 22 pairs. On the contrary, the mouse has only a 20 pairs.

•The rats have a longer gestation period compared with the mice.


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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,Antibiotics, Histamine and antihistamines ,Anticoagulants ,Bronchodilators ,Bioassay of Digitalis. 9


NON – RODENT ANIMAL MODELSRABBIT(Oryctolagus cuniculus)

•Historically, Louis Pasteur used rabbits to develop the rabies vaccine.

•Studies in rabbits are key to many aspects of medical research, including cancer, glaucoma, eye and ear infections, skin conditions, diabetes and emphysema.

•The rabbit has been important in the study of cardiovascular diseases , particularly hypertension and atherosclerosis.

•Enzyme atropine esterase is present in rabbit liver and plasma so it can tolerate large doses of belladona (atropine).

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RABBITS HAVE BEEN USED FOR RESEARCH IN FOLLOWING FIELDS : • Pyrogen testing • Bioassay of anti-diabetic drugs • Screening of agents affecting capillary permeability • Drugs used in glaucoma • Studies related to anti-fertility agents • It has simple cardiac tissue free of connective tissue and hence is

the animal of choice for cardiac studies. •The rabbit has provided an excellent model system to simulate the

response of human tissue to the radiation produced by surgical lasers.

• Laser advancements made possible by research on rabbits include eye surgery and the dissolving of plaque build-up on the walls of arteries.

TESTING OF COSMETICS USING DRAIZE TEST : Rabbits - particularly albino rabbits - are commonly used in testing for

cosmetics and other chemicals, where they are used to perform the Draize test. This test involves the substance being placed on the rabbit's eyes or skin, which are then observed for redness, irritation or any other damage. 11


MONKEY(Macaca mulatta)Used as primate model to

study drug metabolism . •Suitable for undertaking

psycho-pharmacological studies.

•Uterus resembles that of humans, showing regular menstrual cycles.

•Best for studying drugs acting on CNS, CVS, GIT and fertility.

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DOG(Canis familiaris)

•Most preferred large experimental animal due to small alimentary tract and ease of training.

•Used for studying various anti-arrythmic, cardiovascular drugs.

•Mongrel and Beagles are the most preferred due to manageable size, moderate hair coat and docile nature .

• Good model for Diabetes Mellitus, Ulcerative Colitis, Open heart surgery and organ transplantation.

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CREATING TRANSGENIC MODELS

•Zebra fish mutants are currently used to model many human diseases, including Alzheimer’s disease, congenital heart disease, polycystic kidney disease , cancers and development of the nervous system.

•Its aim is to use the zebra fish to produce new disease models, find new drug targets and learn more about the gene-regulation pathways involved in human development and disease.

•Using genetic techniques, a team of researchers stimulated the development of a type of leukaemia - T cell acute lymphoblastic leukaemia - in the fish.

•Creating zebra fish which develop leukaemia will enable researchers to test the effect of various anti-cancer agents.

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ALTERNATIVE APPROACHES TO ANIMAL TESTING

• Russel and burch in 1959 proposed that “if animals were to be used in experiments, every effort should be made to replace them with non‑sentient alternatives”

• They developed the 3R strategy which includes – Refinement- refine experimental methods to decrease

unnecessary pain and trauma to animals – Reduction- reduce the number of animals used in

these experiments – Replacement- replace the animal experiments eg-

computer simulation models, In-vitro methods, cell culture techniques

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METHODS OF REFINEMENT

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Setting the earliest possible end point Using appropriate analgesics and anaesthetics for painful procedure

Use proper handling technique for animals Adequate training prior to performing experiment

Ensure drug doses are correct and drugs are not expired

Perform surgeries and procedure aseptically to prevent infection

METHODS OF REDUCTION• Perform pilot studies • Design studies to use animals as their own

controls eg- Cross over study • Gather data for more than one experiment

concurrently • Consult with statistician and use minimum

number of animals • Minimise variables such as disease, diet,

stress, genetics • Use appropriate species of animals

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METHODS OF REPLACEMENT

• Substitution of insentient material in place of conscious higher animals

• Could be relative or absolute• Replace higher animals with lower animals • Replace live animals with dummies for

teaching and dissection purpose • Use computer simulation and in vitro

methods • Use cell culture and tissue culture

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REFERENCE• A Review on Alternatives to Animal Testing

Methods in Drug Development. Ranganatha N, I. J. Kuppast. International Journal of Pharmacy and Pharmaceutical Sciences.

• www.aboutanimaltesting.co.uk • www.animalresearch.info • Images: Google images• https://en.wikipedia.org/wiki/Model_organism

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https://en.wikipedia.org/wiki/Model_organism

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animal models

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