overview on various animal models to induce different disease conditions

1. EXPERIMENTAL ANIMAL MODEL
FOR INDUCING DIFFERENT
DISEASE CONDITIONS.
Presented by
Dr. Sindhu K.
MVSc Scholar, Dept. of VPT,
COVAS, Pookode.

2. • An animal with a disease either the
same as or like a disease in humans.
• Animal models are used to study the
development and progression of
diseases and to test new treatments
before they are given to humans.
• Animals with transplanted human
cancers or other tissues are called
xenograft models.

3. Anti-inflammatory animal models
Anti-pyretic animal models
Anti-arrhythmic animal models
Anti-hypertensive animal models
Anti-hyperglycemic animal models
Anti-cholesteremic animal models

4. Animal models for CNS activity
Animal models to evaluate Muscle relaxant
activity
Model to evaluate CNS depression & sedation
Animal models for anti-anxiety activity
Anti-convulsant & Anti-epileptic animal models
Analgesic animal models

5. ANTI-INFLAMMATORY MODELS.
• Acute models
• Sub acute models
• Chronic models
• OVA-challenged Mouse Asthma Model
• Acute LPS model
• Chronic LPS Model
• Formalin-induced Chronic Inflammation

6. For
inflammatory
models
Phlogistic agents:
Brewer’s yeast,
formaldehyde, dextran,
egg albumin, kaolin,
Aerosil®, sulfated
polysaccharides like
carrageenan or
naphthoylheparamine.
For edema
models
Histamine, xylene,
arachidonic acid,
phorbol myristate
acetate, oxozolone,
croton oil and formalin.

7. I. ACUTE MODELS
• Carrageenan-induced Paw Edema in Rats
• Histamine Induced Paw Edema in Rats
• Acetic Acid-Induced Vascular Permeability
• Xylene Induced Ear Edema (Thickness and weight parameter)
• Arachidonic Acid-Induced Ear Edema
• Phorbol Myristate Acetate-Induced Ear Edema in Mice
• Myeloperoxidase (MPO) Assay
• Oxazolone-induced Ear Edema in Mice

8. II. SUB-ACUTE MODEL
• Carrageenan Induced Granuloma Pouch Model
• Formalin-induced Paw Edema

9. III. CHRONIC MODEL
• Cotton Pellet-Induced Granuloma in Rats
• The Glass Rod Granuloma

10. ANTI-PYRETIC MODELS

11. BREWERʼS YEAST INDUCED PYREXIA
 Animals should be fasted 6 hrs. before the yeast administration.
 Basal rectal temperature of animals were measured.
 Aqueous 20% w/v of brewer’s yeast in 2% gum acacia @ a dose of 10-
20 mg/kg body weight administered subcutaneous near the
neck/groin of the animals.
 Rectal temperature (RT) after 19 hrs.
 RT increase in at least 0.6 ̊ c is considered as positive.
 RT should be taken after administration of test substance @ 0, 1, 2,
3, 4 & 5 hrs.
 Compare with initial temperature.
 Plot the Graph.

12. LIPOPOLYSACCHARIDE INDUCED
PYREXIA
 Overnight fasting + adlibitum water.
 Inject 0.3 μg/kg lipopolysaccharide (LPS) (from E.
coli) i.v. through the marginal ear vein dilated with
xylene.
 Immediately after administration of LPS, withdraw
food.
 After19 hrs. record rise in rectal temperature.
 RT rise in 0.6 ̊ c or more is considered as positive.
 Record the RT consecutively for 5 hrs.
 Compare recorded with Basal rectal temperatures
(T°C).
 Plot the graph.

13. Anti-
arrhythmic
models
Isolated Cells and
Cell Cultures
Tissue and Organ
Bath Preparations
Langendorff System
(Isolated Heart)
Transgenic models

15. SVT
A regular, abnormally fast heart beat
(tachycardia) caused by rapid firing
of electrical impulses from a focus
above the atrioventricular node (A-V
node) in the heart.
Its called supraventricular because
the tachycardia originates above the
ventricles of the heart.

16. SUPRAVENTRICULAR TACHYCARDIA MODELS.
Wolf-Parkinson –
White syndrome.
Pre excitation
in dogs.
Transgenic mouse
(PRKAG2 over
expression)
Re-entrant arrhythmia
of AV node.
Isolated rabbit heart preparation.
Isolated rabbit heart atrium preparation (AV
node + bundle of HIS)
Blockade of atrial impulse from anterior site
of AV node in dogs.
Isolated canine AV nodal preparation.

17. ATRIAL FLUTTER.
• Atrial flutter is an abnormality in
the beating of the heart. Such
abnormalities, whether in the
rhythm or speed of the heartbeat,
are known as arrhythmias.
• Atrial flutter is similar to atrial
fibrillation, a common heart rhythm
disorder.
• The difference between flutter and
fibrillation is that flutter is well
organized while fibrillation is not.

18. Canine right atrial
crush injury model.
Atrial flutter induced
by Ach & rapid
patching in the dogs.
Atrial flutter by
Aconitine.
Right atrial
enlargement model of
atrial flutter.
Atrial
flutter

19. Atrial fibrillation is an
irregular and often rapid
heart rate that commonly
causes poor blood flow to
the body.
During atrial fibrillation,
the heart's two upper
chambers (the atria) beat
chaotically and irregularly
— out of coordination with
the two lower chambers
(the ventricles) of the heart.

20. ATRIAL FIBRILLATION (AF) MODELS.
AF by atrial ischemia in dogs.
PACAP-27 induced biphasic chronotropic
effect & A.F.
AF in dogs by atrial burst patching.
Vagal AF
AF in isolated Langendorff-perfused rabbit
heart.
AF by fibrillation pacemaker.
AF by Aconitine.
canine model of chronic atrial fibrillation.

21. VENTRICULAR FIBRILLATION MODELS.
VF induced by 60 Hz alternating current in isolated swine right
ventricles.
Ischemia induced ventricular arrhythmia.
Ventricular arrhythmia during exercise by ischemia.
Stretch induced arrhythmias in isolated canine ventricle.
Model for sudden cardiac death.
Canine model of two stage ligation.

22. ANIMAL MODELS OF HYPERTENSION
Renovascular
hypertension
Endocrine
hypertension
Psychogenic
hypertension
Genetic
hypertension
Neurogenic
hypertension
Dietary
hypertension

23. ANIMAL MODELS FOR DIABETES MELLITUS

24. Spontaneous
diabetic models
Obese
ob/ob mouse, KK/Ay
mouse, NZO mouse,
NONcNZO10 mouse,
TSOD mouse, M16
mouse.
Zuffer fatty Rat, ZDF
rat, SHR/N-cp rat,
JCR/LA-cp rat, OLETF
rat, Obese rhesus
monkey.
Non-Obese
Cohen diabetic rat, Torri
rat Non obese C57BL/6.
Akita mutant mouse,
GK rat.

25. DIET/NUTRITION INDUCED DIABETIC ANIMALS
C57/BL 6J mouse.
Spiny mouse.
Sand rat.

26. Chemically induced diabetic animals
Obese
GTG treated
obese mice.
Non obese
Low dose ALX
or STZ adult
rats, mice, etc.

27. Surgical diabetic animals
VMH lesioned
dietary obese
diabetic
animals
Obese
Partial
pancreatectomized
animals e.g. dog,
primate, pig & rats.
Non
obese

28. TRANSGENIC/KNOCK-OUT DIABETIC
ANIMALS.
• β3 receptor knockout mouse
• Uncoupling protein (UCP1)
• Knock-out mouse model
Obese
model
•PPAR-ɣ tissue specific knock out mouse
•Glucokinase or GLUT 2 gene knock out
mice.
•Human islet amyloid polypeptide over
expressed rat (HIP rat)
Non obese
model

29. ANTI-CHOLESTEREMIC ANIMAL MODEL.
Diet induced
hyperlipidemia
(400 mg/kg
cholesterol in 5ml coconut oil)

30. Animal models to evaluate CNS
activity.
Exploratory
behaviour
pattern
Spontaneous
motor activity
Forced motor
activity
General
behavioral
pattern

31. • General behavioral profiles: Awareness, Alertness, Touch
response, Pain response & Sound response.
• Exploratory behavioral pattern evaluation: Y maze test &
Head dip test.
• Spontaneous motor activity: Photoactameter.
• Forced motor activity (muscle relaxant activity): Rota rod test
& Horizontal wire test.

32. Animal models for
muscle relaxant
activity
Traction test
Rota rod test
300 inclined
screen test
Chimney Test
Tail suspension
model of hind limb

33. ANIMAL MODELS FOR CNS DEPRESSION &
SEDATIVE ACTIVITY.
CNS
depression
models
Model to
evaluate
sedative
activity
Antianxiety
models

34. • CNS depression models: Hole cross test & Open field test.
• Antianxiety models: Elevated plus maze test, Hole board
test & Open field test.
• Model to evaluate sedative activity: Barbiturate induced
sleep model.

35. ANIMAL MODELS FOR ANTIANXIETY
ACTIVITIES.
Elevated plus
maze test
Hole board
test
Open field
test

36. ANIMAL MODELS FOR EVALUATION OF
ANTICONVULSANT ACTIVITY &
ANTIEPILEPTIC DRUGS
Anticonvulsant
models.
Seizure models.
• Pentylene tetrazole induced
convulsions
• Maximal electric shock induced
convulsions
• Genetic seizure models
• Photosensitive baboon (Papio papio)
• Mongolian gerbils (Meriones
unguiculatus)

38. ANIMAL MODELS USED IN THE SCREENING
OF ANTIEPILEPTIC DRUGS.
• Genetic seizure models
• Several genetic model of epilepsy validated
using clinically effective drugs (Partial-
onset seizures: Kindling, Status
epilepticus, Senegalese baboons (Papio
papio),Generalized seizures)
• Photosensitive baboon (Papio papio)
• Mongolian gerbils (Meriones unguiculatus)

39. ANALGESIC ACTIVITY
•Tail immersion test
•Tail flick test
(Analgesiometer)

41. REFERENCES.
• Anupama A. Suralkar, Prashant S. Sarda, Mahesh M. Ghaisas, Vishnu N. Thakare, & Dr.
Avinash D. Deshpande. 2012. Lecture notes on inflammation. Dr. D. Y. Patil Institute of
Pharmaceutical Sciences & Research, Pimpri, Pune.
• Bhat L. K., Nandakumar K. and Bhodankar S. L. 2005. Animal models to induce cardiac
arrhythmia. Indian J. Pharmacol. 37(6): 348-357.
• Srinivasan K. & Ramarao P. 2007. Animal models in type 2 diabetes research: An
overview. Indian J Med Res. (1): 451-472.
• Kanakam Vijayabhaskar, Vurugonda Ramadevi, Kalakota Chaitanyaprasad, Sadhiram
Rajeshkumar, Divya Sripada and G. Himabindu. 2014. Evaluation of anti-cholesteremic
and anti-lipidemic activity of seed extract of Achyranthes aspera in diet induced
hyperlipidemia model in rats Journal of Chemical and Pharmaceutical Research.
6(5):1247-1250.
• Google images & Wikipedia.