Clustering autism: Using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity

Academic Article

Abstract

  • 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 Nrxn1╬▒, 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.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 25442038
  • Author List

  • Ellegood J; Anagnostou E; Babineau BA; Crawley JN; Lin L; Genestine M; Dicicco-Bloom E; Lai JKY; Foster JA; Pe├▒agarikano O
  • Start Page

  • 118
  • End Page

  • 125
  • Volume

  • 20
  • Issue

  • 1