Expression of Kruppel-like factor 5 gene in human brain and association of the gene with the susceptibility to schizophrenia.
Genome-wide gene expression analysis using DNA microarray technology is a potential tool to search for unexpected genes that have a susceptibility to schizophrenia. We carried out a microarray analysis in the postmortem prefrontal cortex and found that the expression of the KLF5 gene, whose locus is on 13q21, was down-regulated in schizophrenia patients. This result was confirmed by a Western blot analysis. In a genetic study, we found that a polymorphism of the KLF5 gene (-1593T>C) was associated with schizophrenia. We identified neurons in the prefrontal cortex of human brain as sites of KLF5 expression by in situ hybridization and immunohistochemistry. KLF5 was immunohistochemically localized in granular and pyramidal cells in the hippocampus, which are the principal source of glutamatergic neurotransmission. These findings suggest that the KLF5 gene is a novel schizophrenia-susceptibility gene, and that the expression of the gene is involved in the pathophysiology of schizophrenia via glutamatergic neurotransmission.
Yanagi
Masaya
M
Division of Psychiatry and Neurology, Department of Environmental Health and Safety, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kobe, Japan. myanagi@med.kobe-u.ac.jp
Hashimoto
Takeshi
T
Kitamura
Noboru
N
Fukutake
Masaaki
M
Komure
Osamu
O
Nishiguchi
Naoki
N
Kawamata
Toshio
T
Maeda
Kiyoshi
K
Shirakawa
Osamu
O
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism*; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D035061:Control Groups; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics*
C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors