Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.

Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We...

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Autores principales:	Akiko Watanabe, Tomoko Toyota, Yuji Owada, Takeshi Hayashi, Yoshimi Iwayama, Miho Matsumata, Yuichi Ishitsuka, Akihiro Nakaya, Motoko Maekawa, Tetsuo Ohnishi, Ryoichi Arai, Katsuyasu Sakurai, Kazuo Yamada, Hisatake Kondo, Kenji Hashimoto, Noriko Osumi, Takeo Yoshikawa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/63d30bf2908a4c1ca796853249310795
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spelling	oai:doaj.org-article:63d30bf2908a4c1ca7968532493107952021-11-25T05:33:04ZFabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.1544-91731545-788510.1371/journal.pbio.0050297https://doaj.org/article/63d30bf2908a4c1ca7968532493107952007-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.0050297https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the N-methyl-D-aspartic acid (NMDA) receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming.Akiko WatanabeTomoko ToyotaYuji OwadaTakeshi HayashiYoshimi IwayamaMiho MatsumataYuichi IshitsukaAkihiro NakayaMotoko MaekawaTetsuo OhnishiRyoichi AraiKatsuyasu SakuraiKazuo YamadaHisatake KondoKenji HashimotoNoriko OsumiTakeo YoshikawaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 5, Iss 11, p e297 (2007)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Akiko Watanabe Tomoko Toyota Yuji Owada Takeshi Hayashi Yoshimi Iwayama Miho Matsumata Yuichi Ishitsuka Akihiro Nakaya Motoko Maekawa Tetsuo Ohnishi Ryoichi Arai Katsuyasu Sakurai Kazuo Yamada Hisatake Kondo Kenji Hashimoto Noriko Osumi Takeo Yoshikawa Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.
description	Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the N-methyl-D-aspartic acid (NMDA) receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming.
format	article
author	Akiko Watanabe Tomoko Toyota Yuji Owada Takeshi Hayashi Yoshimi Iwayama Miho Matsumata Yuichi Ishitsuka Akihiro Nakaya Motoko Maekawa Tetsuo Ohnishi Ryoichi Arai Katsuyasu Sakurai Kazuo Yamada Hisatake Kondo Kenji Hashimoto Noriko Osumi Takeo Yoshikawa
author_facet	Akiko Watanabe Tomoko Toyota Yuji Owada Takeshi Hayashi Yoshimi Iwayama Miho Matsumata Yuichi Ishitsuka Akihiro Nakaya Motoko Maekawa Tetsuo Ohnishi Ryoichi Arai Katsuyasu Sakurai Kazuo Yamada Hisatake Kondo Kenji Hashimoto Noriko Osumi Takeo Yoshikawa
author_sort	Akiko Watanabe
title	Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.
title_short	Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.
title_full	Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.
title_fullStr	Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.
title_full_unstemmed	Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.
title_sort	fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/63d30bf2908a4c1ca796853249310795
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Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.

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