Genetic and expression analyses of the STOP (MAP6) gene in schizophrenia.
Accumulating evidence suggests that the pathologic lesions of schizophrenia may in part be due to the altered cytoskeletal architecture of neurons. Microtubule-associated proteins (MAPs) that bind to cytoskeletal microtubules to stabilize their assembly are prominently expressed in neurons. Of the MAPs, MAP6 (STOP) has a particular relevance to schizophrenia pathology, since mice deficient in the gene display neuroleptic-responsive behavioral defects. Here we examined the genetic contribution of MAP6 to schizophrenia in a case (n = 570) -control (n = 570) study, using dense single nucleotide polymorphism (SNP) markers. We detected nominal allelic (p = 0.0291) and haplotypic (global p = 0.0343 for 2 SNP-window, global p = 0.0138 for 3 SNP-window) associations between the 3' genomic interval of the gene and schizophrenia. MAP6 transcripts are expressed as two isoforms. A postmortem brain expression study showed up-regulation of mRNA isoform 2 in the prefrontal cortex (Brodmann's area 46) of patients with schizophrenia. These data suggest that the contribution of MAP6 to the processes that lead to schizophrenia should be further investigated.
Shimizu
Hiromitsu
H
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
Iwayama
Yoshimi
Y
Yamada
Kazuo
K
Toyota
Tomoko
T
Minabe
Yoshio
Y
Nakamura
Kauhiko
K
Nakajima
Mizuho
M
Hattori
Eiji
E
Mori
Norio
N
Osumi
Noriko
N
Yoshikawa
Takeo
T
D000328:Adult; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology
C491894:MAP6 protein, human; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger