05/02/2023
Dr.Ebrahim ali ali AL alfi
Biochemistry level 4 Faculty of science
Mansoura university
Experimental animal models
Animal model :is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of harming an actual human being during the process.
•
• The animal chosen usually meets a determined taxonomic equivalency to humans, so as to react to disease or its treatment in a way that resembles human physiology as needed.
• The use of animal models allows researchers to investigate disease states in ways which would be inaccessible in a human patient, performing procedures on the non-human animal that imply a level of harm that would not be considered ethical to inflict on a human.
• Many drugs, treatments and cures for human diseases have been developed with the use of animal models.
Animal models serving in
research may have an
existing inbred induced diseaseinjury that is similar to a
human condition
There are three main types of animal models
Homologous animals:
same causes, symptoms and
treatment options as would humans who
have the same disease
Isomorphic animals:
share the same symptoms and
treatments
Predictive Animals:
when animals strictly display only the
treatment characteristics of a
disease. This method is commonly used
when researchers do not know the cause
of a disease.
The choice of an animal depends on its suitability for attaining a particular research goal
a) If large amounts of antiserum are sought, rabbit, goat, sheep, or horse might be an appropriate experimental animal.
b) If the goal is development of a protective vaccine, the animal chosen must be susceptible can be mouse, rabbit
c) But if growth of the infectious agent is limited to humans and primates, vaccine development may require the use of monkeys, chimpanzees, or baboons
In vitro assays typically rely on simple interactions of chemicals with a drug target, such as receptor binding or enzyme activity inhibition. However, in vitro results often poorly correlate with in vivo results because the complicated physiological environment is absent in the in vitro testing system.
Commonly Used Lab Animals
Mouse Lifespan: 1-3 years Gestation: 21 days Weaning: 21 days Sexual maturity Females: 6 weeks Males: 8 weeks Estrus: 4-6 days
.
Mouse breeding
Gestation: 21 days Weaning: 21 days Estrus: 4-6 days Sexual maturity
Females: 6 weeks**Males: 8 weeks
Lifespan2-3.5 years
Rat Breeding
Gestation: 30-33 days Parturition = Kindling Weaning: 4-6 weeks Offspring
NZW: 8-10 kitsDutch: 5-6 kits
Ovulation: Coitus Induced Estrus: Continuous Lifespan
NZW: 5-6+ yearsDutch: 5-10+ years
Rabbit Breeding
The Best Part of the Class:
Non-human Primates
Mustela putorius furo Stinky little thieving weasel
Illegal in California“Nail” trims
Use small nail-trim scissors or human nail clips.Blood collection: use chemical restraint
Sample sitesJugular veinCranial vena cava—preferredCephalic vein
Long-gestation period Precocious young
Open-rooted teeth may become maloccluded Fastidious eatersGrass-based commercial pelletVitamin C supplementation:
CANNOT SYTHESIZE THEIR OWN. Must be supplemented.Fresh waterFootpad dermatitis
Ferrets
Guinea Pigs
Hamsters live an average 18 to 24 months and have a gestation period of 16 days.
Active burrowing animals adapted to desert environment.Life span 3.5 yearsProne to autogenic seizuresGood at escapingDiet similar to hamsterNasal dermatitisTyzzer’s disease caused by B. piliformis Never grab gerbil tails: DEGLOVING INJURY
Hamsters
Gerbils
Why mouse preferred?a) The closest to humans –
mammal we share virtually ALL of our genes and use them in similar ways
b) The most complex - integration of systems (endocrine, immune, nervous etc.)
c) ability to quickly multiply, reproducing as often as every nine weeks. generation time is ~ 3 months, so genetics can be done
d) Easy to handle mice are ~ 3 inches long, can keep many mice in a room.
Occupational HealthThree main concerns regarding the use of any lab or exotic animal:
Risk Preventation measures
Allergies Personal Protective Equipment (PPE)Occupational Health Surveillance ProgramThrough Sanitation
Injury PPEProper Handling (Confident handlers!)
Zoonotic Disease PPEThrough sanitationOccupational Health Surveillance Program
Animals are used to understand basic biology, as “models” for studying human biology and disease, and as test subjects for the development and testing of drugs, vaccines, and other biologicals (i.e. antibodies, hormones, ingredients in vaccines, etc.) to improve and advance human health.
The use of genetic engineering—manipulation of an animal’s DNA or genes—is prevalent throughout many fields of research, particularly biomedical. “The mouse has become the flagship of animal testing, especially useful with genetic modifications, gene knock outs [genes are removed], and knock ins [genes are added].
In 2003, NIH [National Institutes of Health] launched the Knock out Mouse Project and has awarded more than $50 million with the goal of creating a library of mouse embryonic stem cells lines, each with a gene knocked out.”
Biomedical Research
animals are subjected to invasive procedures, which can include :Surgeries , traumatic injuries , burns, force-feeding , blood draws , biopsies, Food , water , and social deprivation, dart gun sedation , prolonged restraint , viral and bacterial infections , behavioral and environmental manipulations, and exposure to toxic drugs and chemicals.
Examples include, “creating heart attacks, heart failure, abnormal heart rhythms, strokes, and other cardiovascular traumas in monkeys, dogs, pigs, and other
animals; inducing symptoms of migraines in cats and primates through brain stimulation and manipulation with chemicals; implanting electrodes into the intestines of dogs to
induce motion sickness and vomiting; implanting electrodes into the brains and eyes of monkeys and cats to conduct neurological and vision experiments; and dropping weights
onto rodents to produce spinal cord injuries and paralysis.
In order to create these models,
Anti-inflammatory animal models
Anti-pyretic animal models
Anti-arrhythmic animal models
Anti-hypertensive animal models
Anti-hyperglycemic animal models
Anti-cholestrolemic animal models
uses
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
Rabbit’s sensory system may be studied in basic research; she may be used as a model for eye and skin disorders, or used in eye and skin irritancy tests for environmental toxicity testing.
Dogs, typically young purpose-bred beagles, are commonly used in cardiovascular studies, heart and lung research, genetic studies, age-related research, pulmonary studies, cancer research, and orthopedics, such as the development of prosthetic devices for hip and knee replacements, vertebral fusion models, cervical disc degeneration, etc.
Cats “have long been a mainstay of nih-funded studies of neurological, cardiovascular, and respiratory diseases, and the immune system.” Researchers also use cats in cancer research, genetic disorders, and eye, ear, and infectious disease research.
Nonhuman primates are used in research on vaccines, infectious, cardiovascular, and neurological diseases, aging, reproductive biology, gene therapy, drug addiction, xenotransplantation (cross-species transplants), and vaccine and toxicity testing. The two most common primate species used by far are rhesus , chimpanzees and cynomolgus macaques.
Guinea pigs and hamsters, who are both used a great deal in toxicity testing and as models for infectious, cardiovascular, and neurological diseases, and drug abuse research.
Both mice and rats are heavily used in vaccine and drug research and testing. Birds are used in research on organ development and deformity, visual impairment, muscular
dystrophy, and nutrition, among other things.
As models, scientists aim to produce artificially, a condition in an animal in a laboratory that may resemble the human equivalent of a medical disease or injury.
For example :
Millions of animals and taxpayer dollars are used in the production and testing of biologicals, such as vaccines and antibodies.
For example, a complete batch test for a therapeutic protein can involve 12,000 mice and cost $2.4 million; 2007 estimates for the cost of drug development and to
bring it to market range from $800 million to $1.7 billion. Potential drugs are often required to be tested in at least two animal species in preclinical
trials before moving on to human clinical trials.Yet “only around 5% of drugs that show potential in animal studies ever get licensed for
human use.” Potency tests of such products as vaccines are still based routinely on the principle of
protection, i.e., survival or death after exposure, which was first introduced in the 1890s. Many of these tests are exceptionally cruel, involving high levels of pain and distress for a
range of species from rodents to nonhuman primates (including chimpanzees).
Drug and vaccine development
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