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

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.

• Authors: Hiromitsu Shimizu, Yoshimi Iwayama, Kazuo Yamada, Tomoko Toyota, Yoshio Minabe, Kauhiko Nakamura, Mizuho Nakajima, Eiji Hattori, Norio Mori, Noriko Osumi, Takeo Yoshikawa
• Journal: Schizophrenia research (Schizophr Res) Vol. 84 Issue 2-3 Pg. 244-52 (Jun 2006) ISSN: 0920-9964 [Print] Netherlands
• PMID: 16624526 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MAP6 protein, human
• Microtubule-Associated Proteins
• Protein Isoforms
• RNA, Messenger

Topics

• Adult
• Brain (pathology)
• Case-Control Studies
• Female
• Gene Expression
• Gene Frequency
• Genotype
• Haplotypes
• Humans
• Male
• Microtubule-Associated Proteins (genetics)
• Middle Aged
• Polymorphism, Single Nucleotide
• Protein Isoforms
• RNA, Messenger
• Reverse Transcriptase Polymerase Chain Reaction
• Schizophrenia (genetics, pathology)