Grant sponsor CIHR; Grant number: MOP-106418, Grant sponsor OBI; Grant number: IDS-11-02.
Genetic Effects on Cerebellar Structure Across Mouse Models of Autism Using a Magnetic Resonance Imaging Atlas
Article first published online: 22 OCT 2013
© 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Volume 7, Issue 1, pages 124–137, February 2014
How to Cite
Steadman, P. E., Ellegood, J., Szulc, K. U., Turnbull, D. H., Joyner, A. L., Henkelman, R. M. and Lerch, J. P. (2014), Genetic Effects on Cerebellar Structure Across Mouse Models of Autism Using a Magnetic Resonance Imaging Atlas. Autism Res, 7: 124–137. doi: 10.1002/aur.1344
- Issue published online: 24 FEB 2014
- Article first published online: 22 OCT 2013
- Manuscript Accepted: 17 SEP 2013
- Manuscript Received: 5 MAR 2013
- CIHR. Grant Number: MOP-106418
- OBI. Grant Number: IDS-11-02
- Canadian Foundation for Innovation
- the Ontario Research Fund
- Canada Research Chairs
- Natural Sciences and Engineering Research Council of Canada
- Faculty of Medicine at University of Toronto
- animal models;
- structural MRI;
Magnetic resonance imaging (MRI) of autism populations is confounded by the inherent heterogeneity in the individuals' genetics and environment, two factors difficult to control for. Imaging genetic animal models that recapitulate a mutation associated with autism quantify the impact of genetics on brain morphology and mitigate the confounding factors in human studies. Here, we used MRI to image three genetic mouse models with single mutations implicated in autism: Neuroligin-3 R451C knock-in, Methyl-CpG binding protein-2 (MECP2) 308-truncation and integrin β3 homozygous knockout. This study identified the morphological differences specific to the cerebellum, a structure repeatedly linked to autism in human neuroimaging and postmortem studies. To accomplish a comparative analysis, a segmented cerebellum template was created and used to segment each study image. This template delineated 39 different cerebellar structures. For Neuroligin-3 R451C male mutants, the gray (effect size (ES) = 1.94, FDR q = 0.03) and white (ES = 1.84, q = 0.037) matter of crus II lobule and the gray matter of the paraflocculus (ES = 1.45, q = 0.045) were larger in volume. The MECP2 mutant mice had cerebellar volume changes that increased in scope depending on the genotype: hemizygous males to homozygous females. The integrin β3 mutant mouse had a drastically smaller cerebellum than controls with 28 out of 39 cerebellar structures smaller. These imaging results are discussed in relation to repetitive behaviors, sociability, and learning in the context of autism. This work further illuminates the cerebellum's role in autism. Autism Res 2014, 7: 124–137. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.