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- Title
Clustering autism: using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity.
- Authors
Ellegood, J; Laliberté, C L; van Eede, M C; Tam, E; Osborne, L R; Kouser, M; Espinosa-Becerra, F; Xuan, Z; Powell, C M; Raznahan, A; Robins, D M; Nakai, N; Nakatani, J; Takumi, T; Kerr, T M; Muller, C; Blakely, R D; Veenstra-VanderWeele, J; Henkelman, R M; Lerch, J P
- 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 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.
- Subjects
GENETICS of autism; AUTISM research; NEUROANATOMY; HETEROGENEITY; GENETIC disorder diagnosis; MICE physiology; LABORATORY mice; MAGNETIC resonance imaging
- Publication
Molecular Psychiatry, 2015, Vol 20, Issue 1, p118
- ISSN
1359-4184
- Publication type
Article
- DOI
10.1038/mp.2014.98