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

研究成果: Article

366 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)8987-8992
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
100
発行部数15
DOI
出版物ステータスPublished - 22-07-2003

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Calcineurin
Knockout Mice
Schizophrenia
Dizocilpine Maleate
Phosphoprotein Phosphatases
Calmodulin
Locomotion
Interpersonal Relations
Prosencephalon
Short-Term Memory
Central Nervous System
Calcium

All Science Journal Classification (ASJC) codes

  • General

これを引用

Miyakawa, Tsuyoshi ; Leiter, Lorene M. ; Gerber, David J. ; Gainetdinov, Raul R. ; Sotnikova, Tatyana D. ; Zeng, Hongkui ; Caron, Marc G. ; Tonegawa, Susumu. / Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. :: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 巻 100, 番号 15. pp. 8987-8992.
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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.",
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Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. / Miyakawa, Tsuyoshi; Leiter, Lorene M.; Gerber, David J.; Gainetdinov, Raul R.; Sotnikova, Tatyana D.; Zeng, Hongkui; Caron, Marc G.; Tonegawa, Susumu.

:: Proceedings of the National Academy of Sciences of the United States of America, 巻 100, 番号 15, 22.07.2003, p. 8987-8992.

研究成果: Article

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T1 - Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia

AU - Miyakawa, Tsuyoshi

AU - Leiter, Lorene M.

AU - Gerber, David J.

AU - Gainetdinov, Raul R.

AU - Sotnikova, Tatyana D.

AU - Zeng, Hongkui

AU - Caron, Marc G.

AU - Tonegawa, Susumu

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AB - 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.

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