Genetic and expression analyses of the STOP (MAP6) gene in schizophrenia

Shimizu, Hiromitsu; Iwayama, Yoshimi; Yamada, Kazuo; Toyota, Tomoko; Minabe, Yoshio; Nakamura, Kauhiko; Nakajima, Mizuho; Hattori, Eiji; Mori, Norio; Osumi, Noriko; Yoshikawa, Takeo

doi:10.1016/j.schres.2006.03.017

« Previous Next »Schizophrenia Research
Volume 84, Issue 2 , Pages 244-252, June 2006

Genetic and expression analyses of the STOP (MAP6) gene in schizophrenia

Hiromitsu Shimizu
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
Yoshimi Iwayama
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
Kazuo Yamada
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
Tomoko Toyota
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
Yoshio Minabe
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan
Kauhiko Nakamura
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan
Mizuho Nakajima
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
Eiji Hattori
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
Norio Mori
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan
Noriko Osumi
- Division of Developmental Neuroscience, Center for Translational and Advanced Animal Research, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan
- CREST, Japan Science and Technology Agency, Saitama, Japan
Takeo Yoshikawa
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
- CREST, Japan Science and Technology Agency, Saitama, Japan
- Corresponding author. Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan. Tel.: +81 48 467 5968; fax: +81 48 467 7462.

Received 28 November 2005; received in revised form 6 March 2006; accepted 6 March 2006.

Abstract

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.