Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia.
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.
Miyakawa
Tsuyoshi
T
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
LM
Gerber
David J
DJ
Gainetdinov
Raul R
RR
Sotnikova
Tatyana D
TD
Zeng
Hongkui
H
Caron
Marc G
MG
Tonegawa
Susumu
S
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
D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D000661:Amphetamine; D019703:Calcineurin; D004298:Dopamine