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

Keizo Takao, Tsuyoshi Miyakawa

Research output: Chapter in Book/Report/Conference proceedingConference contribution

36 Citations (Scopus)

Abstract

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.

Original languageEnglish
Title of host publicationIntegrated Molecular Medicine for Neuronal and Neoplastic Disorders
PublisherBlackwell Publishing Inc.
Pages144-159
Number of pages16
ISBN (Print)1573316555, 9781573316552
DOIs
Publication statusPublished - 11-2006
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1086
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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