Investigating gene-to-behavior pathways in psychiatric disorders: The use of a comprehensive behavioral test battery on genetically engineered mice

Keizo Takao, Tsuyoshi Miyakawa

研究成果: Conference contribution

38 被引用数 (Scopus)

抄録

We have been investigating the relationships between genes and behaviors by conducting a systematic and well-defined behavioral test battery with mice that have a mutation on a gene of interest. The behavioral test battery covers a relatively broad range of various behavioral domains such as learning and memory, sensory-motor functions, emotion, motivation, and drug sensitivity/preference. Recently, we subjected mice lacking calcineurin (CN), a calcium/calmodulin protein phosphatase, to the comprehensive behavioral test battery. The mutant mice had a severe working memory deficit, increased locomotor activity, decreased social interaction, and impairments in prepulse and latent inhibition. The abnormalities of CN mutant mice were strikingly similar to those described for schizophrenic patients. Consistent with these findings, human genetics studies in a large sample of affected families detected a significant association of the PPP3CC gene, which encodes the CN gamma catalytic subunit with schizophrenia. The idea that abnormalities in the CN signaling pathway are involved in schizophrenia pathogenesis is consistent with traditional theories of schizophrenia and with many facts known about schizophrenia. A tremendous amount of knowledge about CN has accumulated and, by utilizing this information, the studies on the pathogenesis/pathophysiology of schizophrenia and its related mental disorders will be potentially accelerated. We discuss the potential impact of a large-scale mouse phenotyping project on the study of psychiatric disorders.

本文言語English
ホスト出版物のタイトルIntegrated Molecular Medicine for Neuronal and Neoplastic Disorders
出版社Blackwell Publishing Inc.
ページ144-159
ページ数16
ISBN(印刷版)1573316555, 9781573316552
DOI
出版ステータスPublished - 11-2006
外部発表はい

出版物シリーズ

名前Annals of the New York Academy of Sciences
1086
ISSN(印刷版)0077-8923
ISSN(電子版)1749-6632

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 科学史および科学哲学

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