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.