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Ceramide and metabolites have roles in cell apoptosis and proliferation. We introduced a single\u2010nucleotide mutation identified in human FD patients into the murine\n                    <jats:italic>Asah1<\/jats:italic>\n                    gene to generate the first model of systemic ACDase deficiency. Homozygous\n                    <jats:italic>Asah1<\/jats:italic>\n                    <jats:sup>P361R\/P361R<\/jats:sup>\n                    animals showed ACDase defects, accumulated ceramide, demonstrated FD manifestations and died within 7\u201313 weeks. Mechanistically, MCP\u20101 levels were increased and tissues were replete with lipid\u2010laden macrophages. Treatment of neonates with a single injection of human ACDase\u2010encoding lentivector diminished the severity of the disease as highlighted by enhanced growth, decreased ceramide, lessened cellular infiltrations and increased lifespans. This model of ACDase deficiency offers insights into the pathophysiology of FD and the roles of ACDase, ceramide and related sphingolipids in cell signaling and growth, as well as facilitates the development of therapy.\n                  <\/jats:p>\n                  <jats:p>\n                    \u2192See accompanying article\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1002\/emmm.201302781\" ext-link-type=\"doi\">10.1002\/emmm.201302781<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1002\/emmm.201202301","type":"journal-article","created":{"date-parts":[[2013,5,16]],"date-time":"2013-05-16T06:40:45Z","timestamp":1368686445000},"page":"827-842","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Systemic ceramide accumulation leads to severe and varied pathological consequences"],"prefix":"10.1038","volume":"5","author":[{"given":"Abdulfatah M.","family":"Alayoubi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C. 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