{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:45:21Z","timestamp":1790646321533,"version":"4.1.0"},"reference-count":56,"publisher":"National Academy of Sciences","issue":"31","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,8,2]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>Drosophila porcupine<\/jats:italic>\n                    gene is required for secretion of wingless and other Wnt proteins, and sporadic mutations in its unique human ortholog,\n                    <jats:italic>PORCN<\/jats:italic>\n                    , cause a pleiotropic X-linked dominant disorder, focal dermal hypoplasia (FDH, also known as Goltz syndrome). We generated a conditional allele of the X-linked mouse\n                    <jats:italic>Porcn<\/jats:italic>\n                    gene and analyzed its requirement in Wnt signaling and embryonic development. We find that\n                    <jats:italic>Porcn<\/jats:italic>\n                    -deficient cells exhibit a cell-autonomous defect in Wnt ligand secretion but remain responsive to exogenous Wnts. Consistent with the female-specific inheritance pattern of FDH,\n                    <jats:italic>Porcn<\/jats:italic>\n                    hemizygous male embryos arrest during early embryogenesis and fail to generate mesoderm, a phenotype previously associated with loss of Wnt activity. Heterozygous\n                    <jats:italic>Porcn<\/jats:italic>\n                    mutant females exhibit a spectrum of limb, skin, and body patterning abnormalities resembling those observed in human patients with FDH. Many of these defects are recapitulated by ectoderm-specific deletion of\n                    <jats:italic>Porcn<\/jats:italic>\n                    , substantiating a long-standing hypothesis regarding the etiology of human FDH and extending previous studies that have focused on downstream elements of Wnt signaling, such as \u03b2-catenin. Conditional deletion of\n                    <jats:italic>Porcn<\/jats:italic>\n                    thus provides an experimental model of FDH, as well as a valuable tool to probe Wnt ligand function in vivo.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1006437108","type":"journal-article","created":{"date-parts":[[2011,7,18]],"date-time":"2011-07-18T23:35:45Z","timestamp":1311032145000},"page":"12752-12757","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":162,"title":["Deletion of mouse\n                    <i>Porcn<\/i>\n                    blocks Wnt ligand secretion and reveals an ectodermal etiology of human focal dermal hypoplasia\/Goltz syndrome"],"prefix":"10.1073","volume":"108","author":[{"given":"Jared J.","family":"Barrott","sequence":"first","affiliation":[{"name":"Department of Human Genetics, University of Utah, Salt Lake City, UT 84112; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela M.","family":"Cash","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, Salt Lake City, UT 84112; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron P.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery R.","family":"Barrow","sequence":"additional","affiliation":[{"name":"Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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