Experimental Animal Models Flashcards
Methods of developing animal models
- Spontaneously occurring variations
- Selective breeding
- Genetic modifications
- Drug effects
- Environmental effects
- Surgical & physical alterations
What were the earliest animal models available?
Spontaneously occurring variations within the animal population
What does selective breeding allow?
To keep a trait within a population
Examples of breeding colonies
- Leptin deficient mouse - occurred spontaneously, mice develop symptoms similar to obesity & T2DM
- SHR - selective breeding of WK rats which naturally have HBP
- Nude mouse (athymic mice) - immunocompromised
How is an animal model created by drug effects?
An otherwise healthy animal is treated with a compound known to induce a disease condition or symptoms that closely mimic the disease
Common way to model depression
Chronic mild stress test - animals are subjected to unpredictable stressors resulting in a variety of behavioural deficits: food & water deprivation, small temp reductions, changes of cage mates, changes in light/dark cycles
Examples of drug-induced animal models of disease
- Streptozotocin induced diabetes in rats - IV injection, makes pancreas swell & causes degeneration of islet of Langerhans’ beta cells
- Deoxycorticosterone induced HT in rats, dogs, pigs - prolonged mineralocorticoid admin
- MPTP for PD in primates, nice - admin triggers rapid destruction of DA-synthesising neurons in SN
What is a common model of early life stress?
Maternal separation model - pups separated from mother for several hrs per day over a period i.e. 3hr/day during 1st 2 wks of life
Adults then present with depressive behaviour
How is obesity and metabolic syndrome induced by diet?
- High fat diet fed to rats
- Cafeteria diet: regular chow + ad libitum access to energy dense foods e.g. cookies, cheese, processed meats etc.
Examples of surgical and physical alterations to create animal models of disease
- Ligating or cutting structures - e.g. LCA to generate MI
- Banding or constricting structures - aortic banding leads to cardiac overload, hypertrophy and eventually HF
- Removing organs - pancreatectomy to induce diabetes
Examples of genetic models of disease
- Forward vs reverse genetics
- Microinjection- induced transgenics
- Cre-lox system
Forward vs reverse genetics
Forward: generating spontaneous mutations - not ideal, you can’t target anything, unfair for the animals
Reverse: target specific genes, delete them, see the effects of that change on the phenotype
How does reverse genetics work?
- Inject stem cells into an egg grown by a donor mother
- Mutation incorporated into genome by homologous recombination
- Injected into a foster mother
- Offspring are chimeras - have original and GM genes
- Use selective breeding to get the line you want
How does microinjection-induced transgenics work?
- Obtain eggs
- Eggs fertilised
- Microinjection of manipulated DNA into pronucleus
- If prior to cell division, contributes to all cells of organism
- Fertilised egg then inserted into pseudo pregnant foster mothers
- Mated with vasectomised males - their body then preps for pregnancy
- Offspring are transgenic
Example of a transgenic mouse used in research
SOD1-G93A transgenic mouse model used in ALS (amyotrophic lateral sclerosis) research - display neurodegeneration and symptomatology consistent with ALS
