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

It has been shown that thoracic aortic aneurysm and dissection (TAAD) could be a Mendelian trait caused by a single gene mutation. The LOX gene mutation leads to the development of human TAAD. The LOXL4 gene is a member of the lysyl oxidase gene family. We identified seven variants in the LOXL4 gene...

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Autores principales: Li, Huimin, Guo, Jun, Jia, Yiting, Kong, Wei, Li, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066229/
https://www.ncbi.nlm.nih.gov/pubmed/33807332
http://dx.doi.org/10.3390/genes12040513
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author Li, Huimin
Guo, Jun
Jia, Yiting
Kong, Wei
Li, Wei
author_facet Li, Huimin
Guo, Jun
Jia, Yiting
Kong, Wei
Li, Wei
author_sort Li, Huimin
collection PubMed
description It has been shown that thoracic aortic aneurysm and dissection (TAAD) could be a Mendelian trait caused by a single gene mutation. The LOX gene mutation leads to the development of human TAAD. The LOXL4 gene is a member of the lysyl oxidase gene family. We identified seven variants in the LOXL4 gene in 219 unrelated patients with TAAD by whole-exome sequencing (WES). To further investigate whether LOXL4 is a candidate causative gene for human TAAD, a Loxl4 knockout mouse was generated, and the mutant mice were treated by subcutaneous infusion of angiotensin II. We found that abrogation of Loxl4 did not induce a more severe thoracic or abdominal aortic aneurysm compared with the wild-type C57BL/6J mice. Our results suggest that LOXL4 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.
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spelling pubmed-80662292021-04-25 LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice Li, Huimin Guo, Jun Jia, Yiting Kong, Wei Li, Wei Genes (Basel) Article It has been shown that thoracic aortic aneurysm and dissection (TAAD) could be a Mendelian trait caused by a single gene mutation. The LOX gene mutation leads to the development of human TAAD. The LOXL4 gene is a member of the lysyl oxidase gene family. We identified seven variants in the LOXL4 gene in 219 unrelated patients with TAAD by whole-exome sequencing (WES). To further investigate whether LOXL4 is a candidate causative gene for human TAAD, a Loxl4 knockout mouse was generated, and the mutant mice were treated by subcutaneous infusion of angiotensin II. We found that abrogation of Loxl4 did not induce a more severe thoracic or abdominal aortic aneurysm compared with the wild-type C57BL/6J mice. Our results suggest that LOXL4 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. MDPI 2021-03-31 /pmc/articles/PMC8066229/ /pubmed/33807332 http://dx.doi.org/10.3390/genes12040513 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Huimin
Guo, Jun
Jia, Yiting
Kong, Wei
Li, Wei
LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice
title LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice
title_full LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice
title_fullStr LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice
title_full_unstemmed LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice
title_short LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice
title_sort loxl4 abrogation does not exaggerate angiotensin ii-induced thoracic or abdominal aortic aneurysm in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066229/
https://www.ncbi.nlm.nih.gov/pubmed/33807332
http://dx.doi.org/10.3390/genes12040513
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