Department of Psychiatry, Institute of Human Genetics, The University of Illinois at Chicago, Chicago, IL, USA.
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, and Sangenjaya Station Mental Health Clinic, Tokyo, Japan.
Mol Psychiatry. 2014 Feb;19(2):175-83. doi: 10.1038/mp.2012.185. Epub 2013 Jan 22.
The G72/G30 gene complex is a candidate gene for schizophrenia and bipolar disorder. However, G72 and G30 mRNAs are expressed at very low levels in human brain, with only rare splicing forms observed. We report here G72/G30 expression profiles and behavioral changes in a G72/G30 transgenic mouse model. A human BAC clone containing the G72/G30 genomic region was used to establish the transgenic mouse model, on which gene expression studies, western blot and behavioral tests were performed. Relative to their minimal expression in humans, G72 and G30 mRNAs were highly expressed in the transgenic mice, and had a more complex splicing pattern. The highest G72 transcript levels were found in testis, followed by cerebral cortex, with very low or undetectable levels in other tissues. No LG72 (the long putative isoform of G72) protein was detected in the transgenic mice. Whole-genome expression profiling identified 361 genes differentially expressed in transgenic mice compared with wild-type, including genes previously implicated in neurological and psychological disorders. Relative to wild-type mice, the transgenic mice exhibited fewer stereotypic movements in the open field test, higher baseline startle responses in the course of the prepulse inhibition test, and lower hedonic responses in the sucrose preference test. The transcriptome profile changes and multiple mouse behavioral effects suggest that the G72 gene may play a role in modulating behaviors relevant to psychiatric disorders.
G72/G30 基因复合物是精神分裂症和双相情感障碍的候选基因。然而，G72 和 G30mRNA 在人脑内表达水平极低，仅观察到罕见的剪接形式。我们在此报告 G72/G30 在 G72/G30 转基因小鼠模型中的表达谱和行为改变。使用包含 G72/G30 基因组区域的人类 BAC 克隆建立转基因小鼠模型，对其进行基因表达研究、western blot 和行为测试。与人类的最低表达相比，G72 和 G30mRNA 在转基因小鼠中高度表达，且具有更复杂的剪接模式。G72 转录本水平最高的组织是睾丸，其次是大脑皮层，而在其他组织中则水平极低或无法检测到。在转基因小鼠中未检测到 LG72（G72 的长假定异构体）蛋白。全基因组表达谱分析鉴定出 361 个在转基因小鼠与野生型相比差异表达的基因，包括先前与神经和心理障碍相关的基因。与野生型小鼠相比，转基因小鼠在开阔场测试中的刻板运动减少，在预脉冲抑制测试过程中的基础惊跳反应增高，以及在蔗糖偏好测试中的快感反应降低。转录组谱变化和多种小鼠行为效应提示 G72 基因可能在调节与精神疾病相关的行为方面发挥作用。
