{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:05:37Z","timestamp":1781107537706,"version":"3.54.1"},"reference-count":24,"publisher":"National Academy of Sciences","issue":"52","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,12,28]]},"abstract":"<jats:p>\n                    Zmpste24 is a metalloproteinase required for the processing of prelamin A to lamin A, a structural component of the nuclear lamina.\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    deficiency results in the accumulation of prelamin A within cells, a complete loss of mature lamin A, and misshapen nuclear envelopes.\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    -deficient (\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) mice exhibit retarded growth, alopecia, micrognathia, dental abnormalities, osteolytic lesions in bones, and osteoporosis, which are phenotypes shared with Hutchinson\u2013Gilford progeria syndrome, a human disease caused by the synthesis of a mutant prelamin A that cannot undergo processing to lamin A.\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice also develop muscle weakness. We hypothesized that prelamin A might be toxic and that its accumulation in\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice is responsible for all of the disease phenotypes. We further hypothesized that\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice with half-normal levels of prelamin A (\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice with one\n                    <jats:italic>Lmna<\/jats:italic>\n                    knockout allele) would be subjected to less toxicity and be protected from disease. Thus, we bred and analyzed\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    mice. As expected, prelamin A levels in\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    cells were significantly reduced.\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    mice were entirely normal, lacking all disease phenotypes, and misshapen nuclei were less frequent in\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    cells than in\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    cells. These data suggest that prelamin A is toxic and that reducing its levels by as little as 50% provides striking protection from disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0408558102","type":"journal-article","created":{"date-parts":[[2004,12,17]],"date-time":"2004-12-17T20:17:16Z","timestamp":1103314636000},"page":"18111-18116","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":180,"title":["Heterozygosity for\n                    <i>Lmna<\/i>\n                    deficiency eliminates the progeria-like phenotypes in\n                    <i>Zmpste24<\/i>\n                    -deficient mice"],"prefix":"10.1073","volume":"101","author":[{"given":"Loren G.","family":"Fong","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095; Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; National Cancer Institute, Frederick, MD 21702; and Musculoskeletal and Quantitative Research Group, Department of Radiology, University of California, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095; Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; National Cancer Institute, Frederick, MD 21702; and Musculoskeletal and Quantitative Research Group, Department of Radiology, University of California, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Meta","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095; Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; National Cancer Institute, Frederick, MD 21702; and Musculoskeletal and Quantitative Research Group, Department of Radiology, University of California, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Cot\u00e9","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095; Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; National Cancer Institute, Frederick, MD 21702; and Musculoskeletal and Quantitative Research Group, Department of Radiology, University of California, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao H.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095; Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; National Cancer Institute, Frederick, MD 21702; and Musculoskeletal and Quantitative Research Group, Department of Radiology, University of California, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin L.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095; Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; National Cancer Institute, Frederick, MD 21702; and Musculoskeletal and Quantitative Research Group, Department of Radiology, University of California, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095; Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; National Cancer Institute, Frederick, MD 21702; and Musculoskeletal and Quantitative Research Group, Department of Radiology, University of California, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Burghardt","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095; Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; National Cancer Institute, Frederick, MD 21702; and Musculoskeletal and Quantitative Research Group, Department of Radiology, University of California, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharmila","family":"Majumdar","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095; Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; National Cancer Institute, Frederick, MD 21702; and Musculoskeletal and Quantitative Research Group, Department of Radiology, University of California, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Reue","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095; Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; National Cancer Institute, Frederick, MD 21702; and Musculoskeletal and Quantitative Research Group, Department of Radiology, University of California, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin O.","family":"Bergo","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095; 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