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.
authors.affiliation: 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.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.forename: Lorene M
authors.initials: LM
authors.lastname: Leiter
authors.forename: David J
authors.initials: DJ
authors.lastname: Gerber
authors.forename: Raul R
authors.initials: RR
authors.lastname: Gainetdinov
authors.forename: Tatyana D
authors.initials: TD
authors.lastname: Sotnikova
authors.forename: Hongkui
authors.initials: H
authors.lastname: Zeng
authors.forename: Marc G
authors.initials: MG
authors.lastname: Caron
authors.forename: Susumu
authors.initials: S
authors.lastname: Tonegawa
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D019703:Calcineurin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D012559:Schizophrenia / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D015398:Signal Transduction; D012919:Social Behavior
chemical_list: D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D000661:Amphetamine; D019703:Calcineurin; D004298:Dopamine