Heterozygous disruption of autism susceptibility candidate 2 causes impaired emotional control and cognitive memory

Kei Hori, Taku Nagai, Wei Shan, Asami Sakamoto, Manabu Abe, Maya Yamazaki, Kenji Sakimura, Kiyofumi Yamada, Mikio Hoshino

研究成果: Article査読

10 被引用数 (Scopus)

抄録

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 cytoskelet al 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.

本文言語English
論文番号e0145979
ジャーナルPloS one
10
12
DOI
出版ステータスPublished - 01-12-2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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