Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia

被引:379
作者
Miyakawa, T
Leiter, LM
Gerber, DJ
Gainetdinov, RR
Sotnikova, TD
Zeng, HK
Caron, MG
Tonegawa, S [1 ]
机构
[1] MIT, Howard Hughes Med Inst, Picower Ctr Learning & Memory, Cambridge, MA 02139 USA
[2] MIT, RIKEN MIT Inst Technol Neurosci Res Ctr, Dept Biol, Cambridge, MA 02139 USA
[3] MIT, RIKEN MIT Inst Technol Neurosci Res Ctr, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA
[4] Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Cell Biol, Durham, NC 27710 USA
[5] Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Med, Durham, NC 27710 USA
关键词
D O I
10.1073/pnas.1432926100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:8987 / 8992
页数:6
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