{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:42:06Z","timestamp":1791380526329,"version":"4.3.3"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,2,15]]},"abstract":"<jats:p>\n                    Autosomal dominant polycystic kidney disease (ADPKD), often caused by mutations in the PKD1 gene, is associated with life-threatening vascular abnormalities that are commonly attributed to the frequent occurrence of hypertension. A previously reported targeted mutation of the mouse homologue of PKD1 was not associated with vascular fragility, leading to the suggestion that the vascular lesion may be of a secondary nature. Here we demonstrate a primary role of PKD1 mutations in vascular fragility. Mouse embryos homozygous for the mutant allele (\n                    <jats:italic>\n                      Pkd1\n                      <jats:sup>L<\/jats:sup>\n                    <\/jats:italic>\n                    ) exhibit s.c. edema, vascular leaks, and rupture of blood vessels, culminating in embryonic lethality at embryonic day 15.5. Kidney and pancreatic ductal cysts are present. The\n                    <jats:italic>Pkd1<\/jats:italic>\n                    -encoded protein, mouse polycystin 1, was detected in normal endothelium and the surrounding vascular smooth muscle cells. These data reveal a requisite role for polycystin 1 in maintaining the structural integrity of the vasculature as well as epithelium and suggest that the nature of the PKD1 mutation contributes to the phenotypic variance in ADPKD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.040550097","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"1731-1736","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":274,"title":["Polycystin 1 is required for the structural integrity of blood vessels"],"prefix":"10.1073","volume":"97","author":[{"given":"Keetae","family":"Kim","sequence":"first","affiliation":[{"name":"Renal Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; and Genzyme Corp., Framingham, MA 01701"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Drummond","sequence":"additional","affiliation":[{"name":"Renal Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; and Genzyme Corp., Framingham, MA 01701"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oxana","family":"Ibraghimov-Beskrovnaya","sequence":"additional","affiliation":[{"name":"Renal Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; and Genzyme Corp., Framingham, MA 01701"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Klinger","sequence":"additional","affiliation":[{"name":"Renal Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; and Genzyme Corp., Framingham, MA 01701"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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