LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice

• Main Authors: Huimin Li, Jun Guo, Yiting Jia, Wei Kong, Wei Li
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Genes
• Subjects: angiotensin II; <i>LOXL4</i>; thoracic or abdominal aortic aneurysm; variants; whole-exome sequencing
• Online Access: https://www.mdpi.com/2073-4425/12/4/513
• ISSN: 2073-4425

It has been shown that thoracic aortic aneurysm and dissection (TAAD) could be a Mendelian trait caused by a single gene mutation. The <i>LOX</i> gene mutation leads to the development of human TAAD. The <i>LOXL4</i> gene is a member of the lysyl oxidase gene family. We identified seven variants in the <i>LOXL4</i> gene in 219 unrelated patients with TAAD by whole-exome sequencing (WES). To further investigate whether <i>LOXL4</i> is a candidate causative gene for human TAAD, a <i>LOXL4</i> knockout mouse was generated, and the mutant mice were treated by subcutaneous infusion of angiotensin II. We found that abrogation of <i>LOXL4</i> did not induce a more severe thoracic or abdominal aortic aneurysm compared with the wild-type C57BL/6J mice. Our results suggest that <i>LOXL4</i> 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.