Roles of interferon-gamma and its target genes in schizophrenia: Proteomics-based reverse genetics from mouse to human

• Published in: Proteomics (Weinheim) 2012-06, Vol.12 (11), p.1815-1829
• Main Authors: Kim, Hak-Jae, Eom, Chi-Yong, Kwon, Joseph, Joo, Jaesoon, Lee, Sujeong, Nah, Seong-Su, Kim, Il-Chul, Jang, Ik-Soon, Chung, Young-Ho, Kim, Seung Il, Chung, Joo-Ho, Choi, Jong-Soon
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Biomedicine; Brain; Brain - metabolism; Case-Control Studies; Creatine kinase; Creatine Kinase, BB Form - genetics; Creatine Kinase, BB Form - metabolism; Data processing; Down-Regulation; Female; Fundamental and applied biological sciences. Psychology; gamma -Interferon; Gels; Gene polymorphism; Genes; Genetics; Genomics; Humans; Immunoblotting; Interferon gamma; Interferon-gamma - genetics; Interferon-gamma - metabolism; Male; Medical sciences; Mental disorders; Mice; Mice, Inbred C57BL; Mice, Knockout; Miscellaneous; Phosphate; Polymerase chain reaction; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Promoters; Proteins; Proteome - analysis; Proteomics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Republic of Korea; Reverse Genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Schizophrenia; Schizophrenia - genetics; Schizophrenia - metabolism; Single nucleotide polymorphism; Therapeutic applications; Triose-Phosphate Isomerase - genetics; Triose-Phosphate Isomerase - metabolism; Up-Regulation
• ISSN: 1615-9853; 1862-8346; 1615-9861
• DOI: 10.1002/pmic.201100184

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.