RNA metabolism and dysmyelination in schizophrenia

Decreased expression of a subset of oligodendrocyte and myelin-related genes is the most consistent finding among gene expression studies of postmortem brain tissue from subjects with schizophrenia (SCZ), although heritable variants have yet to be found that can explain the bulk of this data. However, expression of the glial gene Quaking (QKI), encoding an RNA binding (RBP) essential for myelination, was recently found to be decreased in SCZ brain. Both oligodendrocyte/myelin related genes, and other RBPs that are known or predicted to be targets of QKI, are also decreased in SCZ. Two different quaking mutant mice share some pathological features in common with SCZ, including decreased expression of myelin-related genes and dysmyelination, without gross destruction of white matter. Therefore, although these mice are not a model of SCZ per se, understanding the similarities and differences in gene expression between brains from these mice and subjects with SCZ could help parse out distinct genetic pathways underlying SCZ.