title: Heterozygous Disruption of Autism susceptibility candidate 2 Causes Impaired Emotional Control and Cognitive Memory.
abstract: Mutations in the Autism susceptibility candidate 2 gene (AUTS2) have been associated with a broad range of psychiatric illnesses including autism spectrum disorders, intellectual disability and schizophrenia. We previously demonstrated that the cytoplasmic AUTS2 acts as an upstream factor for the Rho family small GTPase Rac1 and Cdc42 that regulate the cytoskeletal rearrangements in neural cells. Moreover, genetic ablation of the Auts2 gene in mice has resulted in defects in neuronal migration and neuritogenesis in the developing cerebral cortex caused by inactivation of Rac1-signaling pathway, suggesting that AUTS2 is required for neural development. In this study, we conducted a battery of behavioral analyses on Auts2 heterozygous mutant mice to examine the involvement of Auts2 in adult cognitive brain functions. Auts2-deficient mice displayed a decrease in exploratory behavior as well as lower anxiety-like behaviors in the absence of any motor dysfunction. Furthermore, the capability for novel object recognition and cued associative memory were impaired in Auts2 mutant mice. Social behavior and sensory motor gating functions were, however, normal in the mutant mice as assessed by the three-chamber test and prepulse inhibition test, respectively. Together, our findings indicate that AUTS2 is critical for the acquisition of neurocognitive function.
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Hori
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Wei
authors.initials: W
authors.lastname: Shan
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan.
authors.forename: Asami
authors.initials: A
authors.lastname: Sakamoto
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Hoshino
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D003071:Cognition; D003598:Cytoskeletal Proteins; D004644:Emotions; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D008297:Male; D008568:Memory; D051379:Mice; D023421:Models, Animal; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D012919:Social Behavior; D014157:Transcription Factors
chemical_list: C554283:AUTS2 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; D014157:Transcription Factors