Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia

Tsuyoshi Miyakawa, Lorene M. Leiter, David J. Gerber, Raul R. Gainetdinov, Tatyana D. Sotnikova, Hongkui Zeng, Marc G. Caron, Susumu Tonegawa

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Abstract

Calcineurin (CN), a calcium- and calmodulin-dependent protein phosphatase, plays a significant role in the central nervous system. Previously, we reported that forebrain-specific CN knockout mice (CN mutant mice) have impaired working memory. To further analyze the behavioral effects of CN deficiency, we subjected CN mutant mice to a comprehensive behavioral test battery. Mutant mice showed increased locomotor activity, decreased social interaction, and impairments in prepulse inhibition and latent inhibition. In addition, CN mutant mice displayed an increased response to the locomotor stimulating effects of MK-801. Collectively, the abnormalities of CN mutant mice are strikingly similar to those described for schizophrenia. We propose that alterations affecting CN signaling could comprise a contributing factor in schizophrenia pathogenesis.

Original languageEnglish
Pages (from-to)8987-8992
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number15
DOIs
Publication statusPublished - 22-07-2003

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