title: Roles of interferon-gamma and its target genes in schizophrenia: Proteomics-based reverse genetics from mouse to human.
abstract: A decreased production of interferon gamma (IFNG) has been observed in acute schizophrenia. In order to explore the possible relationship between IFNG and schizophrenia, we attempted to analyze the differentially expressed proteins in the brains of interferon-gamma knockout (Ifng-KO) mice. Five upregulated and five downregulated proteins were identified with 2D gels and MALDI-TOF/TOF MS analyses in Ifng-KO mouse brain. Of the identified proteins, we focused on creatine kinase brain (CKB) and triose phosphate isomerase 1 (TPI1). Consistent with the proteomic data, reverse transcriptase-mediated PCR, immunoblotting, and immunohistochemistry analyses confirmed that the levels of gene expressions of Ckb and Tpi1 were downregulated and upregulated, respectively. When we analyzed the genetic polymorphisms of the single nucleotide polymorphisms (SNPs) of their human orthologous genes in a Korean population, the promoter SNPs of CKB and TPI1 were weakly associated with schizophrenia. In addition, IFNG polymorphisms were associated with schizophrenia. These results suggest that IFNG and proteins affected by IFNG may play a role in the pathogenesis of schizophrenia.
authors.affiliation: Soonchunhyang Medical Research Institute, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Kim
authors.forename: Chi-Yong
authors.initials: CY
authors.lastname: Eom
authors.forename: Joseph
authors.initials: J
authors.lastname: Kwon
authors.forename: Jaesoon
authors.initials: J
authors.lastname: Joo
authors.forename: Sujeong
authors.initials: S
authors.lastname: Lee
authors.forename: Seong-Su
authors.initials: SS
authors.lastname: Nah
authors.forename: Il-Chul
authors.initials: IC
authors.lastname: Kim
authors.forename: Ik-Soon
authors.initials: IS
authors.lastname: Jang
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Chung
authors.forename: Seung Il
authors.initials: SI
authors.lastname: Kim
authors.forename: Joo-Ho
authors.initials: JH
authors.lastname: Chung
authors.forename: Jong-Soon
authors.initials: JS
authors.lastname: Choi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D052276:Creatine Kinase, BB Form / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020543:Proteome / Q000032:analysis; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D056910:Republic of Korea; D059386:Reverse Genetics; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism*; D014305:Triose-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D020543:Proteome; D012333:RNA, Messenger; D007371:Interferon-gamma; D052276:Creatine Kinase, BB Form; D014305:Triose-Phosphate Isomerase