Investigating genes-to-behaviors pathways in psychiatric diseases: An approach using a comprehensive behavioral test battery on genetically engineered mice

Keizo Takao, Tsuyoshi Miyakawa

Research output: Contribution to journalShort survey

2 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
Pages (from-to)135-142
Number of pages8
JournalJapanese Journal of Neuropsychopharmacology
Volume28
Issue number3
Publication statusPublished - 01-06-2008

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Calcineurin
Psychiatry
Schizophrenia
Genes
Phosphoprotein Phosphatases
Memory Disorders
Medical Genetics
Calmodulin
Locomotion
Interpersonal Relations
Short-Term Memory
Mental Disorders
Motivation
Catalytic Domain
Emotions
Behavior Rating Scale
Learning
Calcium
Mutation
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

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