Lecture 7 animal models Flashcards
Why use mice in research?
- Ethical necessity
- Control
- Highly conserved pathways
- Cost and time effective
What are some commonly used species in research?
- Drosophila
- Zebrafish
- Mice
- Rats
- Non-human primates
Model generation using genetic methods
- Transgenic
- Knockout/in
- CRISPR-Cas9
Model generation using pharmacological methods
Neurotoxins or vector-based
Model generation using surgical/lesion methods
- Arterial occlusion for stroke
- compression injury of spinal cord
Model generation using environmental or behavioural manipulation
Early maternal separation - how this affects neurodevelopment
* Stress, diet, hypoxia/ischemia, sleep deprivation, social isolation
What are some other ways models are generated?
Autoimmune/inflammatory
Humanised
Spontaneous - not intentionally generated
What is face validity?
How much does the model “look like” the real thing
What is construct validity?
Does the animal recapitulate the cause or pathophysiology of disease
What is predictuve validity?
Does the animal respond to treatments in a way that parallels human outcomes?
3 R’s of animal research
- Reduce no. animals used
- Refine to cause less stress
- Replace animal methods where possible
Why is a researchers ethical responsibility so important?
Ensure humane treatment and reproducibility of results
What are some thinsg researchers also need to consider when handle animals
- Severity of procedures
- Pain and distress - what kinds and how
- Long-term housing and well being
- End-of-Life decisions
What types of neurodevelopmental animal models exist?
Autism, schizophrenia and intellectual disabilities have models in ALL of the mentioned animals
Mice are used for Down Syndrome
Dysmetria
Over/under-shooting movements
Ataxia
Uncoordinated movements
Shaker Rats
Tremor, ataxia
* Mostly males
* Lose purkinje cells in cerebellum
Gene identification in shaker rats
FRAMESHIFT mutation Slc9a6 encoding NHE6
* associated with Christianson syndrome
Where is NHE6 expressed?
Expressed in cerebellum (Purkinje cells), hippocampus, and frontal cortex.
What symptoms occur when there is no functional Slc9a6?
- Ataxia (Cerebellum)
- Cognitive deficits (Frontal Cx.)
- Epilepsy (Hippo.)
- Autism (Cere. AND Front. Cx.)
- Postnatal microcephaly
What is an adeno-associated virus?
Small, non-replicating virus used fo gene delivery
* Used to drive expression of interest gene
* Use promotor
