{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:49:10Z","timestamp":1787017750773,"version":"build-2736575974"},"reference-count":36,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DK078314"],"award-info":[{"award-number":["R01DK078314"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32DK007126"],"award-info":[{"award-number":["T32DK007126"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"\n The glomerular basement membrane (GBM) is a critical component of the kidney\u2019s blood filtration barrier. Alport syndrome, a hereditary disease leading to kidney failure, is caused by the loss or dysfunction of the GBM\u2019s major collagen type IV (COL4) isoform \u03b1\n 3<\/jats:sub>\n \u03b1\n 4<\/jats:sub>\n \u03b1\n 5<\/jats:sub>\n . The constituent COL4 \u03b1-chains assemble into heterotrimers in the endoplasmic reticulum before secretion into the extracellular space. If any one of the \u03b1\n 3<\/jats:sub>\n -, \u03b1\n 4<\/jats:sub>\n -, or \u03b1\n 5<\/jats:sub>\n -chains is lost due to mutation of one of the genes, then the entire heterotrimer is lost. Patients with Alport syndrome typically have mutations in the X-linked COL4A5 gene or uncommonly have the autosomal recessive form of the disease due to COL4A3 or COL4A4 mutations. Treatment for Alport syndrome is currently limited to angiotensin-converting enzyme inhibition or angiotensin receptor blockers. Experimental approaches in Alport mice have demonstrated that induced expression of COL4A3, either widely or specifically in podocytes of Col4a3\n \u2212\/\u2212<\/jats:sup>\n mice, can abrogate disease progression even after establishment of the abnormal GBM. While targeting podocytes in vivo for gene therapy is a significant challenge, the more accessible glomerular endothelium could be amenable for mutant gene repair. In the present study, we expressed COL4A3 in Col4a3\n \u2212\/\u2212<\/jats:sup>\n Alport mice using an endothelial cell-specific inducible transgenic system, but collagen-\u03b1\n 3<\/jats:sub>\n \u03b1\n 4<\/jats:sub>\n \u03b1\n 5<\/jats:sub>\n (IV) was not detected in the GBM or elsewhere, and the Alport phenotype was not rescued. Our results suggest that endothelial cells do not express the Col4a3\/a4\/a5 genes and should not be viewed as a target for gene therapy.\n <\/jats:p>","DOI":"10.1152\/ajprenal.00556.2018","type":"journal-article","created":{"date-parts":[[2019,2,6]],"date-time":"2019-02-06T08:16:57Z","timestamp":1549441017000},"page":"F830-F837","source":"Crossref","is-referenced-by-count":20,"title":["Endothelial cell-specific collagen type IV-\u03b1\n 3<\/sub>\n expression does not rescue Alport syndrome in\n \n Col4a3\n \u2212<\/sup>\n <\/i>\n \/\u2212<\/sup>\n mice"],"prefix":"10.1152","volume":"316","author":[{"given":"Steven D.","family":"Funk","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond H.","family":"Bayer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Washington 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