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Mol Psychiatry. 2015 Feb;20(1):118-25. doi: 10.1038/mp.2014.98. Epub 2014 Sep 9.

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

Author information

1
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada.
2
Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
3
Laboratory of Behavioral Neurosciences, National Institute of Mental Health, Bethesda, MD, USA.
4
1] Laboratory of Behavioral Neurosciences, National Institute of Mental Health, Bethesda, MD, USA [2] Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California Davis School of Medicine, Sacramento, CA, USA.
5
Department of Neurosciences and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA.
6
The Brain-Body Institute, McMaster University, Hamilton, ON, Canada.
7
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
8
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
9
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
10
Departments of Medicine and Molecular Genetics, University of Toronto, Toronto, ON, Canada.
11
Departments of Neurology and Neurotherapeutics, Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
12
Child Psychiatry Branch, National Institutes of Mental Health, Bethesda, MD, USA.
13
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA.
14
Department of Mental Biology, RIKEN Brain Science Institute, Wako, Japan.
15
Department of Pharmacology, Vanderbilt Kennedy Center, Vanderbilt Brain Institute, Nashville, TN, USA.
16
1] Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.

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.

PMID:
25199916
PMCID:
PMC4426202
DOI:
10.1038/mp.2014.98
[Indexed for MEDLINE]
Free PMC Article

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