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

Ellegood J, Anagnostou E, Babineau BA, Crawley JN, Lin L, Genestine M, DiCicco-Bloom E, Lai JK, Foster JA, Peñagarikano O, Geschwind DH, Pacey LK, Hampson DR, Laliberté CL, Mills AA, Tam E, Osborne LR, Kouser M, Espinosa-Becerra F, Xuan Z, Powell CM, Raznahan A, Robins DM, Nakai N, Nakatani J, Takumi T, van Eede MC, Kerr TM, Muller C, Blakely RD, Veenstra-VanderWeele J, Henkelman RM, Lerch JP
Mol Psychiatry. 2015 20 (1): 118-25

PMID: 25199916 · PMCID: PMC4426202 · DOI:10.1038/mp.2014.98

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.

MeSH Terms (11)

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

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