McInnes L Alison, Lauriat Tara L
Department of Psychiatry and Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Neurosci Biobehav Rev. 2006;30(4):551-61. doi: 10.1016/j.neubiorev.2005.10.003. Epub 2006 Jan 30.
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.
少突胶质细胞和髓鞘相关基因子集的表达降低是精神分裂症（SCZ）患者死后脑组织基因表达研究中最一致的发现，尽管尚未发现可解释这些数据大部分的遗传变异。然而，最近发现，在SCZ脑内，编码髓鞘形成所必需的RNA结合蛋白（RBP）的胶质基因震颤蛋白（QKI）的表达降低。少突胶质细胞/髓鞘相关基因以及已知或预测为QKI靶点的其他RBP在SCZ中也降低。两种不同的震颤蛋白突变小鼠与SCZ有一些共同的病理特征，包括髓鞘相关基因表达降低和髓鞘形成异常，而没有白质的严重破坏。因此，尽管这些小鼠本身不是SCZ模型，但了解这些小鼠与SCZ患者大脑之间基因表达的异同可能有助于梳理出SCZ潜在的不同遗传途径。
