Increased Dosage of High-Affinity Kainate Receptor Gene grik4 Alters Synaptic Transmission and Reproduces Autism Spectrum Disorders Features.
M Isabel AllerValeria PecoraroAna V PaternainSantiago CanalsJuan LermaPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2016)
A genetic overlap exists between autism spectrum disorders (ASD), currently thought to represent a continuum of the same disorder with varying degrees of severity, and other neurodevelopmental and neuropsychiatric endophenotypes. We show that the duplication of a single gene coding for a high-affinity kainate receptor subunit (i.e., grik4) in a limited area of the brain recapitulates behavioral endophenotypes seen in humans diagnosed with autism (anhedonia, depression, anxiety, and altered social interaction), including some humans with GRIK4 duplications. Therefore, it should be possible to use mice overexpressing grik4 to directly address circuit dysfunctions associated with ASDs and test specific treatments of autism-related behaviors.
Keyphrases
- autism spectrum disorder
- intellectual disability
- genome wide
- copy number
- attention deficit hyperactivity disorder
- sleep quality
- genome wide identification
- healthcare
- depressive symptoms
- mental health
- white matter
- resting state
- high fat diet induced
- binding protein
- gene expression
- transcription factor
- subarachnoid hemorrhage