Liu Cong, Hu Qian, Chen Yan, Wu Lingqian, Liu Xionghao, Liang Desheng
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha 410008, China.
Brain Sci. 2021 Mar 29;11(4):436. doi: 10.3390/brainsci11040436.
Since the first report that Stxbp6, a brain-enriched protein, regulates the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, little has been discovered about its functions over the past two decades. To determine the effects of Stxbp6 loss on nervous-system-associated phenotypes and underlying mechanisms, we constructed a global Stxbp6-knockout mouse. We found that Stxbp6-null mice survive normally, with normal behavior, but gained less weight relative to age- and sex-matched wildtype mice. RNA-seq analysis of the cerebral cortex of Stxbp6-null mice relative to wildtype controls identified 126 differentially expressed genes. Of these, 57 were upregulated and 69 were downregulated. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the most significant enriched KEGG term was "complement and coagulation cascades". Our results suggest some potential regulatory pathways of Stxbp6 in the central nervous system, providing a remarkable new resource for understanding Stxbp6 function at the organism level.
自从首次报道大脑富集蛋白Stxbp6调节可溶性N - 乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）复合物的组装以来，在过去二十年中，关于其功能的发现甚少。为了确定Stxbp6缺失对神经系统相关表型及潜在机制的影响，我们构建了全基因组Stxbp6敲除小鼠。我们发现，Stxbp6基因敲除小鼠能正常存活，行为正常，但相对于年龄和性别匹配的野生型小鼠体重增加较少。对Stxbp6基因敲除小鼠与野生型对照小鼠的大脑皮质进行RNA测序分析，鉴定出126个差异表达基因。其中，57个上调，69个下调。此外，京都基因与基因组百科全书（KEGG）富集分析表明，最显著富集的KEGG术语是“补体和凝血级联反应”。我们的结果提示了Stxbp6在中枢神经系统中的一些潜在调控途径，为在生物体水平理解Stxbp6的功能提供了重要的新资源。
