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

Ellegood, J., Anagnostou, E., Babineau, B. A., Crawley, J. N., Lin, L., Genestine, M., DiCicco-Bloom, E., Lai, J. K., Foster, J. A., Penagarikano, O., Geschwind, D. H., Pacey, L. K., Hampson, D. R., Laliberte, C. L., Mills, A. A., 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., van Eede, M. C., Kerr, T. M., Muller, C., Blakely, R. D., Veenstra-VanderWeele, J., Henkelman, R. M., Lerch, J. P. (2015) Clustering autism: using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity. Mol Psychiatry, 20 (1). pp. 118-125. ISSN 1359-4184

URL: http://www.ncbi.nlm.nih.gov/pubmed/25199916
DOI: 10.1038/mp.2014.98

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 Nrxn1alpha, 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.

Item Type: Paper
Subjects: diseases & disorders > mental disorders > personality disorders > autism
organs, tissues, organelles, cell types and functions > organs types and functions > brain
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
organism description > model organism
organism description > animal > mammal > rodent > mouse
CSHL Authors:
Communities: CSHL labs > Mills lab
Depositing User: Matt Covey
Date Deposited: 24 Sep 2014 14:06
Last Modified: 02 Feb 2017 16:16
PMCID: PMC4426202
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30810

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