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Neuroscience. 2016 Mar 24;318:12-21. doi: 10.1016/j.neuroscience.2016.01.021. Epub 2016 Jan 12.

Regional brain volumes changes in adult male FMR1-KO mouse on the FVB strain.

Author information

1
Department of Psychiatry and Behavioural Neuroscience, McMaster University, Brain-Body Institute, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada. Electronic address: jon.lai@yorku.ca.
2
Department of Medical Biophysics, University of Toronto, Mouse Imaging Centre, Hospital for Sick Children, 25 Orde Street, Toronto, Ontario M5T 3H7, Canada. Electronic address: jason@phenogenomics.ca.
3
Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada. Electronic address: doering@mcmaster.ca.
4
Department of Psychiatry and Behavioural Neuroscience, McMaster University, Brain-Body Institute, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada. Electronic address: jfoster@mcmaster.ca.
5
Department of Medical Biophysics, University of Toronto, Mouse Imaging Centre, Hospital for Sick Children, 25 Orde Street, Toronto, Ontario M5T 3H7, Canada. Electronic address: jacob@mouseimaging.ca.

Abstract

Fragile X Syndrome (FXS) is the most common heritable single gene cause of autism spectrum disorder (ASD). FMR1-KO mice mimic the etiology and phenotypic manifestations of FXS. Neuroanatomical changes in specific brain regions have been reported in clinical settings and in preclinical models. FMR1-KO mice have been generated in different strains including C57Bl/6 (B6) and FVB. Mice on different genetic backgrounds have stable yet distinct behavioral phenotypes that may lead to unique gene-strain interactions on brain structure. Previous magnetic resonance imaging (MRI) studies have examined FMR1 knockout male mice on a B6 and found few differences compared to wild-type mice. Here, we examine brain volumes in FMR1 knockout male mice on a FVB background using high resolution (multi-channel 7.0Tesla) MRI. We observe multiple differences in the neuroanatomy of male FMR1-/y mice on a FVB background. Significantly larger relative volume (% total brain volume) differences were found in major white matter structures throughout the brain. In addition, there were changes in areas associated with fronto-striatal circuitry and other regions. Functional and structural connectivity differences are often seen in human ASD, and therefore, this increased white matter seen in the FMR1-KO-FVB could be highlighting a structural over-connectivity, which could lead to some of the behavioral abnormalities seen with the FMR1-KO-FVB mice. Furthermore, these results highlight the importance of genetic strain contribution to brain structure.

KEYWORDS:

autism spectrum disorder; genetic mouse model; regional brain volumes

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