L12 - Autism mouse models Flashcards
What are 3 facets of Autism spectrum disorder?
Social interaction
communication
reprtitve/restricted behaviours - serious enough to effect everyday life
What are the co-mordbidities of ASD?
GIT symptoms
sleep disorders
seizures
aggression
axiety
motor disorders - distinctive gait
sensory deficits (90%)
ASD affects about __% of school aged children
1.5%
True or false
ASD is Heterogenous and a lifelong disorder
true
Which functional gene groups are implicated in ASD?
Sex hormones - e.g estrogen receptor
social responsivity
Neural development and connectivity (Neuroligin-3)
immune pathways - IL10
Metabolism
Why do we use mice in brain research?
They have a six layered neocortex
short breeding and lifespans
mice are inbred and geneticially identical, can assess effect of environmental factors
can look at the molecular basis of neurological disease with invasive techniques
What are the Advantages of mouse models?
Genome accessible for manipulation
Difficult to model entire spectrum of disease phenotypes but can focus on specific traits or ‘‘endophenotypes’’ of the disorders
- communication
- repetitive actions
- social behaviour
IN EXAM
What makes a good mouse model?
face validity
- Endophenotypes: eg: Behavioural traits similar to patients
Construct validity
- Biological dysfunction: eg Gene mutations found in patients
Predictive validity
- response to treatments: eg atypical antipscychotics
How to study behaviour in mouse models of autism?
Social interaction
communication
repetitive behavious
associated symptoms: sezures, anxiety, sleep disruption etc..
How do you measure social interaction in mouse?
3 chamber test
agression = resident intruder test
How do you measure brain mechanisms in mouse autims models?
Electrophysiology - EEG
molcular biology - single cell RT-PCR
Anatomy - biocytin labelling, immunochemistry
fMRI
What is the Neuroligin-3 mouse (NL3) model of autism?
Neuroligin-3 is a postsynaptic adhesion moelcule which mediates synaptic signalling via binding to neurexins
This is reduced in the model, - same amount of mRNA but in the processing the concenrtation at the synapse is reduced
has incerased aggression phenotype
What are the anxiety tests for mouse?
elevated plus maze
light-dark box
true or false
in the resident intruder test, mutatnt NL3 muce are quicker to attack
true
What rescues the enhanced agression in NL3 mice?
risperidone
