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Gorlin syndrome (GS) is an autosomal dominant disorder wherein affected individuals develop multiple basal cell carcinomas (BCCs) of the skin. We developed a murine model of Ptch1 haploinsufficiency on an ornithine decarboxylase (ODC) transgenic background (<jats:italic>Ptch1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>\/ODC<jats:sup>t<\/jats:sup>\/C57BL\/6) that is more sensitive to BCCs growth as compared with <jats:italic>Ptch1<\/jats:italic><jats:sup>+\/+<\/jats:sup>\/ODC<jats:sup>t<\/jats:sup>\/C57BL\/6 littermates. <jats:italic>Ptch1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>\/ODC<jats:sup>t<\/jats:sup>\/C57BL\/6 mice show an altered metabolic landscape in the phenotypically normal skin, including restricted glucose availability, restricted ribose\/deoxyribose flow and NADPH production, an accumulation of \u03b1-ketoglutarate, aconitate, and citrate that is associated with reversal of the tricarboxylic acid cycle, coupled with increased ketogenic\/lipogenic activity via acetyl-CoA, 3-hydroybutyrate, and cholesterol metabolites. Also apparent was an increased content\/acetylation of amino-acids, glutamine and glutamate, in particular. Accordingly, metabolic alterations due to a single copy loss of <jats:italic>Ptch1<\/jats:italic> in <jats:italic>Ptch1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>\/ODC<jats:sup>t<\/jats:sup>\/C57BL\/6 heterozygous mice may provide insights about the cancer prone phenotype of BCCs in GS patients, including biomarkers\/targets for early intervention.<\/jats:p>","DOI":"10.1038\/s41598-019-49470-w","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T10:03:36Z","timestamp":1568109816000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Patched1 haploinsufficiency severely impacts intermediary metabolism in the skin of Ptch1+\/\u2212\/ODC transgenic mice"],"prefix":"10.1038","volume":"9","author":[{"given":"Changzhao","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahendra","family":"Kashyap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiping","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4083-1998","authenticated-orcid":false,"given":"Shaida A.","family":"Andrabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahid M.","family":"Mukhtar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna L.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Bickers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levy","family":"Kopelovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Athar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,10]]},"reference":[{"key":"49470_CR1","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1001\/jamadermatol.2015.1187","volume":"151","author":"HW Rogers","year":"2015","unstructured":"Rogers, H. 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