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Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia.


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.

SUBMITTER: Miyakawa T 

PROVIDER: S-EPMC166425 | biostudies-literature | 2003 Jul

REPOSITORIES: biostudies-literature

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Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia.

Miyakawa Tsuyoshi T   Leiter Lorene M LM   Gerber David J DJ   Gainetdinov Raul R RR   Sotnikova Tatyana D TD   Zeng Hongkui H   Caron Marc G MG   Tonegawa Susumu S  

Proceedings of the National Academy of Sciences of the United States of America 20030708 15


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 lat  ...[more]

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