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This disorder is characterized by arteriovenous malformations that are prone to rupture, and the ensuing hemorrhages are responsible for iron-deficiency anemia. Along with activin receptor-like kinase (ALK1), mutations in endoglin are associated with the vast majority of HHT cases. In this study, we characterized the zebrafish endoglin locus and demonstrated that it produces two phylogenetically conserved protein isoforms. Functional analysis of a CRISPR\/Cas9 zebrafish endoglin mutant revealed that Endoglin deficiency is lethal during the course from juvenile stage to adulthood. Endoglin-deficient zebrafish develop cardiomegaly, resulting in heart failure and hypochromic anemia, which both stem from chronic hypoxia. endoglin mutant zebrafish display structural alterations of the developing gills and underlying vascular network that coincide with hypoxia. Finally, phenylhydrazine treatment demonstrated that lowering hematocrit\/blood viscosity alleviates heart failure and enhances the survival of Endoglin-deficient fish. Overall, our data link Endoglin deficiency to heart failure and establish zebrafish as a valuable HHT model.<\/jats:p>","DOI":"10.1242\/dmm.049488","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T05:38:33Z","timestamp":1683610713000},"source":"Crossref","is-referenced-by-count":8,"title":["Deficiency in hereditary hemorrhagic telangiectasia-associated Endoglin elicits hypoxia-driven heart failure in zebrafish"],"prefix":"10.1242","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0452-1578","authenticated-orcid":false,"given":"Etienne","family":"Leli\u00e8vre","sequence":"first","affiliation":[{"name":"LPHI, INSERM, CNRS, Universit\u00e9 de Montpellier 1 , 34095 Montpellier , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2095-6670","authenticated-orcid":false,"given":"Charlotte","family":"Bureau","sequence":"additional","affiliation":[{"name":"LPHI, INSERM, CNRS, Universit\u00e9 de Montpellier 1 , 34095 Montpellier , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8616-6498","authenticated-orcid":false,"given":"Yann","family":"Bordat","sequence":"additional","affiliation":[{"name":"LPHI, INSERM, CNRS, Universit\u00e9 de Montpellier 1 , 34095 Montpellier , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-1333","authenticated-orcid":false,"given":"Maxence","family":"Fr\u00e9taud","sequence":"additional","affiliation":[{"name":"INRAE, Universit\u00e9 Paris-Saclay, VIM 3 , 78350 Jouy-en-Josas , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6013-4460","authenticated-orcid":false,"given":"Christelle","family":"Langevin","sequence":"additional","affiliation":[{"name":"INRAE, Universit\u00e9 Paris-Saclay, IERP 4 , 78350 Jouy-en-Josas , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0950-0063","authenticated-orcid":false,"given":"Chris","family":"Jopling","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9nomique Fonctionnelle, Universit\u00e9 de Montpellier, CNRS, INSERM LabEx ICST 2 , 34094 Montpellier , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7683-3661","authenticated-orcid":false,"given":"Karima","family":"Kissa","sequence":"additional","affiliation":[{"name":"LPHI, INSERM, CNRS, Universit\u00e9 de Montpellier 1 , 34095 Montpellier , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"2023060207350198100_DMM049488C1","first-page":"191","article-title":"Hypoxia regulates the natriuretic peptide system","volume":"3","author":"Arjamaa","year":"2011","journal-title":"Int. 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