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Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.

Original publication

DOI

10.1038/mp.2014.98

Type

Journal article

Journal

Mol Psychiatry

Publication Date

02/2015

Volume

20

Pages

118 - 125

Keywords

Animals, Autistic Disorder, Brain, Disease Models, Animal, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Mice, Mice, Inbred BALB C, Mice, Transgenic, Multigene Family