title: Regional brain volumes changes in adult male FMR1-KO mouse on the FVB strain.
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.
authors.affiliation: 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.
authors.forename: J K Y
authors.initials: JK
authors.lastname: Lai
authors.affiliation: 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.
authors.forename: J P
authors.initials: JP
authors.lastname: Lerch
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada. Electronic address: doering@mcmaster.ca.
authors.forename: L C
authors.initials: LC
authors.lastname: Doering
authors.affiliation: 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.
authors.forename: J A
authors.initials: JA
authors.lastname: Foster
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Ellegood
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D010641:Phenotype
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse
keywords: autism spectrum disorder; genetic mouse model; regional brain volumes