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PMID: 12851457 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 15 ·2003-07-22 ·Pages 8987-92

Miyakawa T, Leiter LM, Gerber DJ, Gainetdinov RR, Sotnikova TD, Zeng H, Caron MG, Tonegawa S

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.

MeSH Terms
Amphetamine/pharmacology Animals Behavior, Animal Calcineurin/deficiency,genetics,physiology Corpus Striatum/drug effects,physiopathology Disease Models, Animal Dizocilpine Maleate/pharmacology Dopamine/physiology Glutamic Acid/physiology Humans Male Mice Mice, Inbred C57BL Mice, Knockout Motor Activity/drug effects Schizophrenia/etiology,genetics,physiopathology Signal Transduction Social Behavior
Chemicals
Glutamic Acid Dizocilpine Maleate Amphetamine Calcineurin Dopamine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Miyakawa Tsuyoshi
Howard Hughes Medical Institute, The Picower Center for Learning and Memory and RIKEN/Massachusetts Institute of Technology Neuroscience Research Center, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Leiter Lorene M
Gerber David J
Gainetdinov Raul R
Sotnikova Tatyana D
Zeng Hongkui
Caron Marc G
Tonegawa Susumu
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1432926100
Published
2003-07-22
Epub
2003-00-08
Pages
8987-92
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC166425
Subset
IM
Grants
NIMH NIH HHS · P50 MH058880 · United States
NIMH NIH HHS · MH58880-03 · United States
External Links
PubMed source DOI: 10.1073/pnas.1432926100 PMC Full Text View journal details
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