Schizophrenia (SZ) is a serious and disabling mental disorder with a lifetime prevalence of about 1% of the population worldwide, and commonly has a chronic course. The underlying pathological mechanisms are still largely unknown, but a growing body of evidence suggests that it is a multifactorial disorder influenced by genetic, neurodevelopmental and social factors. Disrupted-in-schizophrenia 1 (DISC1) is a gene disrupted by a (1;11) (q42.1;q14.3) translocation that segregates with major psychiatric disorders including schizophrenia, recurrent major depression and bipolar affective disorder in a Scottish family. Here we report that DBZ (DISC1 Binding Zinc-finger protein), a brain-specific member of DISC1 interactome, positively regulates oligodendrocyte differentiation. In an in vitro oligodendrocyte primary culture, the expression of DBZ was increased after induction of differentiation of oligodendrocyte by deprivation of PDGF and siRNA knockdown of DBZ decreased the expression level of myelin related markers such as MBP, MAG and CNPase. In mouse corpus callosum, DBZ mRNA expression in oligodendrocyte was intense at P7, the period of myelination, and it was hardly detectable in adult by in situ hybridization. Furthermore, a delay of oligodendrocyte maturation in DBZ knockout mice was revealed by the electron microscope analysis. These results indicate that DBZ is involved in oligodendrocyte differentiation. As multiple lines of evidence obtained by brain imaging, studies in postmortem brains and genetic association studies have implicated oligodendrocytes and myelin dysfunction in SZ, these results may provide important clue about the
underlying etiology of SZ.