title: Deficiency of schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia.
abstract: Schnurri-2 (Shn-2), an nuclear factor-κB site-binding protein, tightly binds to the enhancers of major histocompatibility complex class I genes and inflammatory cytokines, which have been shown to harbor common variant single-nucleotide polymorphisms associated with schizophrenia. Although genes related to immunity are implicated in schizophrenia, there has been no study showing that their mutation or knockout (KO) results in schizophrenia. Here, we show that Shn-2 KO mice have behavioral abnormalities that resemble those of schizophrenics. The mutant brain demonstrated multiple schizophrenia-related phenotypes, including transcriptome/proteome changes similar to those of postmortem schizophrenia patients, decreased parvalbumin and GAD67 levels, increased theta power on electroencephalograms, and a thinner cortex. Dentate gyrus granule cells failed to mature in mutants, a previously proposed endophenotype of schizophrenia. Shn-2 KO mice also exhibited mild chronic inflammation of the brain, as evidenced by increased inflammation markers (including GFAP and NADH/NADPH oxidase p22 phox), and genome-wide gene expression patterns similar to various inflammatory conditions. Chronic administration of anti-inflammatory drugs reduced hippocampal GFAP expression, and reversed deficits in working memory and nest-building behaviors in Shn-2 KO mice. These results suggest that genetically induced changes in immune system can be a predisposing factor in schizophrenia.
authors: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.
authors: Keizo
authors: K
authors: Takao
authors: Katsunori
authors: K
authors: Kobayashi
authors: Hideo
authors: H
authors: Hagihara
authors: Koji
authors: K
authors: Ohira
authors: Hirotaka
authors: H
authors: Shoji
authors: Satoko
authors: S
authors: Hattori
authors: Hisatsugu
authors: H
authors: Koshimizu
authors: Juzoh
authors: J
authors: Umemori
authors: Keiko
authors: K
authors: Toyama
authors: Hironori K
authors: HK
authors: Nakamura
authors: Mahomi
authors: M
authors: Kuroiwa
authors: Jun
authors: J
authors: Maeda
authors: Kimie
authors: K
authors: Atsuzawa
authors: Kayoko
authors: K
authors: Esaki
authors: Shun
authors: S
authors: Yamaguchi
authors: Shigeki
authors: S
authors: Furuya
authors: Tsuyoshi
authors: T
authors: Takagi
authors: Noah M
authors: NM
authors: Walton
authors: Nobuhiro
authors: N
authors: Hayashi
authors: Hidenori
authors: H
authors: Suzuki
authors: Makoto
authors: M
authors: Higuchi
authors: Nobuteru
authors: N
authors: Usuda
authors: Tetsuya
authors: T
authors: Suhara
authors: Akinori
authors: A
authors: Nishi
authors: Mitsuyuki
authors: M
authors: Matsumoto
authors: Shunsuke
authors: S
authors: Ishii
authors: Tsuyoshi
authors: T
authors: Miyakawa
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D004268:DNA-Binding Proteins / Q000172:deficiency*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C490430:Hivep2 protein, mouse
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