Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Capital Medical University, Center of Rare Diseases, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100019, China.
Genes (Basel). 2021 Mar 31;12(4):513. doi: 10.3390/genes12040513.
It has been shown that thoracic aortic aneurysm and dissection (TAAD) could be a Mendelian trait caused by a single gene mutation. The gene mutation leads to the development of human TAAD. The gene is a member of the lysyl oxidase gene family. We identified seven variants in the gene in 219 unrelated patients with TAAD by whole-exome sequencing (WES). To further investigate whether is a candidate causative gene for human TAAD, a knockout mouse was generated, and the mutant mice were treated by subcutaneous infusion of angiotensin II. We found that abrogation of did not induce a more severe thoracic or abdominal aortic aneurysm compared with the wild-type C57BL/6J mice. Our results suggest that may not play a major role in the development of angiotensin II-induced aortic aneurysm. The functional study using this animal model system is important for the evaluation of candidate genes of TAAD identified by WES.
已经表明，胸主动脉瘤和夹层（TAAD）可能是一种由单个基因突变引起的孟德尔性状。该基因突变导致人类 TAAD 的发生。该基因是赖氨酰氧化酶基因家族的成员。我们通过全外显子组测序（WES）在 219 名无关联的 TAAD 患者中鉴定出 基因中的 7 种变体。为了进一步研究 是否是人类 TAAD 的候选致病基因，我们生成了 基因敲除小鼠，并通过皮下输注血管紧张素 II 对突变小鼠进行处理。我们发现，与野生型 C57BL/6J 小鼠相比， 基因缺失并没有诱导更严重的胸主动脉或腹主动脉瘤。我们的结果表明， 在血管紧张素 II 诱导的主动脉瘤的发展中可能不起主要作用。使用这种动物模型系统进行的功能研究对于评估 WES 鉴定的 TAAD 的候选基因很重要。
