title: RacGAP α2-chimaerin function in development adjusts cognitive ability in adulthood.
abstract: A major concern in neuroscience is how cognitive ability in adulthood is affected and regulated by developmental mechanisms. The molecular bases of cognitive development are not well understood. We provide evidence for the involvement of the α2 isoform of Rac-specific guanosine triphosphatase (GTPase)-activating protein (RacGAP) α-chimaerin (chimerin) in this process. We generated and analyzed mice with global and conditional knockouts of α-chimaerin and its isoforms (α1-chimaerin and α2-chimaerin) and found that α-chimaerin plays a wide variety of roles in brain function and that the roles of α1-chimaerin and α2-chimaerin are distinct. Deletion of α2-chimaerin, but not α1-chimaerin, beginning during early development results in an increase in contextual fear learning in adult mice, whereas learning is not altered when α2-chimaerin is deleted only in adulthood. Our findings suggest that α2-chimaerin acts during development to establish normal cognitive ability in adulthood.
authors.affiliation: Division of Neurogenetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan; Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Iwata
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohi
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Masuda
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Iwama
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Department of Molecular Neuropsychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan. Electronic address: sitohara@brain.riken.jp.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.affiliation: Division of Neurogenetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan; Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan. Electronic address: tiwasato@nig.ac.jp.
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwasato
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D020848:Chimerin 1 / Q000235:genetics / Q000378:metabolism*; D003071:Cognition; D003214:Conditioning, Classical; D005239:Fear; D051379:Mice; D008810:Mice, Inbred C57BL; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D020848:Chimerin 1; D020033:Protein Isoforms