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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.

Original publication

DOI

10.1002/aur.1344

Type

Journal article

Journal

Autism Res

Publication Date

02/2014

Volume

7

Pages

124 - 137

Keywords

animal models, genetics, neuroanatomy, neuroimaging, structural MRI, Animals, Brain Mapping, Cell Adhesion Molecules, Neuronal, Cerebellum, Child Development Disorders, Pervasive, DNA Mutational Analysis, Disease Models, Animal, Female, Gene Knock-In Techniques, Genotype, Homozygote, Integrin beta3, Magnetic Resonance Imaging, Male, Membrane Proteins, Methyl-CpG-Binding Protein 2, Mice, Mice, Knockout, Mice, Neurologic Mutants, Nerve Tissue Proteins, Organ Size, Reference Values, Sex Factors