title: Behavioral and neuroanatomical analyses in a genetic mouse model of 2q13 duplication.
abstract: Duplications of human chromosome 2q13 have been reported in patients with neurodevelopmental disorder including autism spectrum disorder. Nephronophthisis-1 (NPHP1) was identified as a causative gene in the minimal deletion on chromosome 2q13 for familial juvenile type 1 nephronophthisis and Joubert syndrome, an autosomal recessive neurodevelopmental disorder characterized by a cerebellar and brain stem malformation, hypotonia, developmental delay, ataxia, and sometimes associated with cognitive impairment. NPHP1 encodes a ciliary protein, nephrocystin-1, which is expressed in the brain, yet its function in the brain remains largely unknown. In this study, we generated bacterial artificial chromosome-based transgenic mice, called 2q13 dup, that recapitulate human chromosome 2q13 duplication and contain one extra copy of the Nphp1 transgene. To analyze any behavioral alterations in 2q13 dup mice, we conducted a battery of behavioral tests. Although 2q13 dup mice show no significant differences in social behavior, they show deficits in spontaneous alternation behavior and fear memory. We also carried out magnetic resonance imaging to confirm whether copy number gain in this locus affects the neuroanatomy. There was a trend toward a decrease in the cerebellar paraflocculus of 2q13 dup mice. This is the first report of a genetic mouse model for human 2q13 duplication.
authors.affiliation: RIKEN Brain Science Institute (BSI), Wako, Saitama, 351-0198, Japan.|Graduate School of Biomedical Sciences, Hiroshima University, Minami, Hiroshima, 734-8553, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kishimoto
authors.affiliation: RIKEN Brain Science Institute (BSI), Wako, Saitama, 351-0198, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nomura
authors.affiliation: Mouse Imaging Centre (MICe), Hospital for Sick Children, Toronto, ON, M5T 3H7, Canada.
authors.forename: Jacob
authors.initials: J
authors.lastname: Ellegood
authors.affiliation: RIKEN Brain Science Institute (BSI), Wako, Saitama, 351-0198, Japan.|Graduate School of Biomedical Sciences, Hiroshima University, Minami, Hiroshima, 734-8553, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Fukumoto
authors.affiliation: Mouse Imaging Centre (MICe), Hospital for Sick Children, Toronto, ON, M5T 3H7, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, ON, M5S 1A1, Canada.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lerch
authors.affiliation: Division of Child and Adolescent Psychiatry, Department of Psychiatry and Human Behavior, Brown University, Providence, RI, 02908, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Moreno-De-Luca
authors.affiliation: Institute Pasteur, Paris, 75015, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bourgeron
authors.affiliation: RIKEN Brain Science Institute (BSI), Wako, Saitama, 351-0198, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Tamada
authors.affiliation: RIKEN Brain Science Institute (BSI), Wako, Saitama, 351-0198, Japan.|Graduate School of Biomedical Sciences, Hiroshima University, Minami, Hiroshima, 734-8553, Japan.
authors.forename: Toru
authors.identifier: http://orcid.org/0000-0001-7153-266X
authors.initials: T
authors.lastname: Takumi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D058674:Chromosome Duplication; D002875:Chromosomes / Q000235:genetics*; D003598:Cytoskeletal Proteins; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005239:Fear; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012919:Social Behavior
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C534985:Nphp1 protein, mouse