{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:30:15Z","timestamp":1781109015976,"version":"3.54.1"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"42","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,10,16]]},"abstract":"<jats:p>\n                    Lipodystrophies are syndromes of adipose tissue degeneration associated with severe defects in lipid and glucose homeostasis. We report here the generation and analysis of\n                    <jats:italic>\n                      Pparg\n                      <jats:sup>ldi<\/jats:sup>\n                    <\/jats:italic>\n                    , a targeted allele that confers conditional dominant lipodystrophy in mice. The\n                    <jats:italic>\n                      Pparg\n                      <jats:sup>ldi<\/jats:sup>\n                    <\/jats:italic>\n                    allele was generated by insertion of the Tet activator (tTA) and a tTA-regulated\n                    <jats:italic>Flag-Pparg1<\/jats:italic>\n                    transgene into the\n                    <jats:italic>Pparg<\/jats:italic>\n                    gene. Unexpectedly, tTA elicits mild lipodystrophy, insulin resistance, and dyslipidemia, and the Flag-PPAR\u03b31 transgene surprisingly exacerbates these traits. Doxycycline can both completely prevent and reverse these phenotypes, providing a mouse model of inducible lipodystrophy. Embryonic fibroblasts from either\n                    <jats:italic>Pparg<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>ldi<\/jats:italic>\n                      \/+\n                    <\/jats:sup>\n                    or the phenotypically similar\n                    <jats:italic>aP2-nSrebp1c<\/jats:italic>\n                    (\n                    <jats:italic>Sr<\/jats:italic>\n                    ) transgenic mice undergo robust adipogenesis, suggesting that neither strain develops lipodystrophy because of defective adipocyte differentiation. In addition,\n                    <jats:italic>Pparg<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>ldi<\/jats:italic>\n                      \/+\n                    <\/jats:sup>\n                    adipose tissue shares extensive gene expression aberrations with that of\n                    <jats:italic>Sr<\/jats:italic>\n                    mice, authenticating the phenotype at the molecular level and revealing a common expression signature of lipodystrophic fat. Thus, the\n                    <jats:italic>Pparg<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>ldi<\/jats:italic>\n                      \/+\n                    <\/jats:sup>\n                    mouse provides a conditional animal model for studying lipodystrophy and its associated physiology and gene expression.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0707797104","type":"journal-article","created":{"date-parts":[[2007,10,5]],"date-time":"2007-10-05T20:34:35Z","timestamp":1191616475000},"page":"16627-16632","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":33,"title":["A mouse model of conditional lipodystrophy"],"prefix":"10.1073","volume":"104","author":[{"given":"Suyeon","family":"Kim","sequence":"first","affiliation":[{"name":"*The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Wen","family":"Huang","sequence":"additional","affiliation":[{"name":"*The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy J.","family":"Snow","sequence":"additional","affiliation":[{"name":"*The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly","family":"Ablamunits","sequence":"additional","affiliation":[{"name":"St. Luke's\u2013Roosevelt Hospital Center and Columbia University,404 West 114th Street, New York, NY 10025"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneer G.","family":"Hasham","sequence":"additional","affiliation":[{"name":"*The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy H.","family":"Young","sequence":"additional","affiliation":[{"name":"*The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelique C.","family":"Paulk","sequence":"additional","affiliation":[{"name":"*The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel E.","family":"Richardson","sequence":"additional","affiliation":[{"name":"*The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason P.","family":"Affourtit","sequence":"additional","affiliation":[{"name":"*The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tali","family":"Shalom-Barak","sequence":"additional","affiliation":[{"name":"*The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol J.","family":"Bult","sequence":"additional","affiliation":[{"name":"*The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaacov","family":"Barak","sequence":"additional","affiliation":[{"name":"*The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609; 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