title: Neuroanatomical Phenotypes Are Consistent With Autism-Like Behavioral Phenotypes in the 15q11-13 Duplication Mouse Model.
abstract: Paternally and maternally inherited deletions and duplications of human chromosome 15q11-13 are relatively common in the human population. Furthermore, duplications in the 15q region are often associated with autism. Both maternal and paternal interstitial 15q11-13 duplication mouse models have been previously created, where several behavioral differences were found in the paternal duplication (patDp/+) mouse but not in the maternal duplication (matDp/+). These included decreased sociability, behavioral inflexibility, abnormal ultrasonic vocalizations, decreased spontaneous activity, and increased anxiety. Similarly, in the current study, we found several anatomical differences in the patDp/+ mice that were not seen in the matDp/+ mice. Regional differences that are evident only in the paternal duplication are a smaller dentate gyrus and smaller medial striatum. These differences may be responsible for the behavioral inflexibility. Furthermore, a smaller dorsal raphe nucleus could be responsible for the reported serotonin defects. This study highlights consistency that can be found between behavioral and anatomical phenotyping.
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario Canada (J.E., R.M.H., J.L.).
authors.forename: Jacob
authors.initials: J
authors.lastname: Ellegood
authors.affiliation: RIKEN Brain Science Institute, Wako, Saiama, Japan (N.N., T.T.).
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nakai
authors.affiliation: Shiga University of Medical Science, Ohtsu, Shiga, Japan (J.N.).
authors.forename: Jin
authors.initials: J
authors.lastname: Nakatani
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario Canada (J.E., R.M.H., J.L.).|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada (R.M.H., J.L.).
authors.forename: Mark
authors.initials: M
authors.lastname: Henkelman
authors.affiliation: RIKEN Brain Science Institute, Wako, Saiama, Japan (N.N., T.T.).|JST, CREST(T.T.).
authors.forename: Toru
authors.initials: T
authors.lastname: Takumi
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario Canada (J.E., R.M.H., J.L.).|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada (R.M.H., J.L.).
authors.forename: Jason
authors.initials: J
authors.lastname: Lerch
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D010641:Phenotype
keywords: 15q11-13 duplication; animal models; copy number variation; molecular genetics; neuroanatomy; structural MRI