The presence of pronounced impairments in several domains in NRXN1α KO rats clearly suggests that nonsocial cognitive deficits can also be measured in an animal model of ASD.
The two deletions upstream of the NRXN1 gene were found to segregate with psychiatric disorders in the family and further similar deletions have been observed in patients diagnosed with autism spectrum disorder.
The spectrum of phenotypes associated with heterozygous deletions of neurexin-1 (NRXN1) is diverse and includes: autism spectrum disorder, attention deficit hyperactivity disorder, intellectual disability, seizures, schizophrenia, mood disorders and congenital malformations.
To better understand the degree and extent to which individual genes associated with ASD differ in their contribution to global measures of white matter microstructure, diffusion tensor imaging (DTI) was acquired from three novel rat genetic models of ASD (Fmr1, Nrxn1, and Pten) and DTI parameters of fractional anisotropy, mean, axial, and radial diffusivity were measured.
Here, we examined the synaptic effects of rat Mint2 N723S mutation (equivalent to autism-linked human MINT2 N722S mutation) which targets a conserved asparagine residue in the second PDZ domain of Mint2 that binds to neurexin-1α (Nrxn1α), a presynaptic cell-adhesion protein implicated in ASDs.
We generated human iPS derived neural stem cells and differentiated cells from healthy control individuals and an individual with autism spectrum disorder carrying bi-allelic NRXN1-alpha deletion.
NRXN1 copy number variation is a rare genetic factor commonly shared among autism spectrum disorder (ASD), schizophrenia, intellectual disability, epilepsy and developmental delay.
These are the first experimental data that associate a deletion of Neurexin 1α with alterations in behaviours relevant to autism spectrum disorder across development and highlight the importance of assessing the developmental trajectory in mouse models of neurodevelopmental disorders.This article is protected by copyright.All rights reserved.