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

Research output: Contribution to journalArticle

370 Citations (Scopus)

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

Fingerprint

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

Cite this

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. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 15. pp. 8987-8992.
@article{7ac41d48d97848499c849e446fdc56f7,
title = "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.",
author = "Tsuyoshi Miyakawa and Leiter, {Lorene M.} and Gerber, {David J.} and Gainetdinov, {Raul R.} and Sotnikova, {Tatyana D.} and Hongkui Zeng and Caron, {Marc G.} and Susumu Tonegawa",
year = "2003",
month = "7",
day = "22",
doi = "10.1073/pnas.1432926100",
language = "English",
volume = "100",
pages = "8987--8992",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "15",

}

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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 15, 22.07.2003, p. 8987-8992.

Research output: Contribution to journalArticle

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.

UR - http://www.scopus.com/inward/record.url?scp=0042202625&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042202625&partnerID=8YFLogxK

U2 - 10.1073/pnas.1432926100

DO - 10.1073/pnas.1432926100

M3 - Article

C2 - 12851457

AN - SCOPUS:0042202625

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

SN - 0027-8424

IS - 15

ER -