Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA.
Sci Rep. 2019 Mar 25;9(1):5070. doi: 10.1038/s41598-019-41592-5.
Following ischemic stroke, the penumbra, at-risk neural tissue surrounding the core infarct, survives for a variable period of time before progressing to infarction. We investigated genetic determinants of the size of penumbra in mice subjected to middle cerebral artery occlusion (MCAO) using a genome-wide approach. 449 male mice from 33 inbred strains underwent MCAO for 6 hours (215 mice) or 24 hours (234 mice). A genome-wide association study using genetic data from the Mouse HapMap project was performed to examine the effects of genetic variants on the penumbra ratio, defined as the ratio of the infarct volume after 6 hours to the infarct volume after 24 hours of MCAO. Efficient mixed model analysis was used to account for strain interrelatedness. Penumbra ratio differed significantly by strain (F = 2.7, P < 0.001) and was associated with 18 significant SNPs, including 6 protein coding genes. We have identified 6 candidate genes for penumbra ratio: Clint1, Nbea, Smtnl2, Rin3, Dclk1, and Slc24a4.
缺血性脑卒中后，核心梗死周围的半影区（处于危险中的神经组织）在进展为梗死之前，可存活一段时间。我们使用全基因组方法研究了中脑动脉闭塞（MCAO）小鼠半影区大小的遗传决定因素。33 个近交系的 449 只雄性小鼠接受 MCAO 6 小时（215 只小鼠）或 24 小时（234 只小鼠）。使用来自 Mouse HapMap 项目的遗传数据进行全基因组关联研究，以检查遗传变异对半影区比例的影响，半影区比例定义为 6 小时 MCAO 后梗死体积与 24 小时 MCAO 后梗死体积的比值。高效混合模型分析用于解释品系间的相关性。半影区比例因品系而异（F=2.7，P<0.001），与 18 个显著的 SNP 相关，包括 6 个蛋白编码基因。我们已经确定了半影区比例的 6 个候选基因：Clint1、Nbea、Smtnl2、Rin3、Dclk1 和 Slc24a4。
