TY - JOUR
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
PY - 2003/7/22
Y1 - 2003/7/22
N2 - 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.
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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U2 - 10.1073/pnas.1432926100
DO - 10.1073/pnas.1432926100
M3 - Article
C2 - 12851457
AN - SCOPUS:0042202625
SN - 0027-8424
VL - 100
SP - 8987
EP - 8992
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
ER -