{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:35:13Z","timestamp":1791423313166,"version":"4.3.3"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,10]]},"abstract":"<jats:p>\n                    Zmpste24 is an integral membrane metalloproteinase of the endoplasmic reticulum. Biochemical studies of tissues from\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    -deficient mice (\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) have indicated a role for Zmpste24 in the processing of\n                    <jats:italic>CAAX<\/jats:italic>\n                    -type prenylated proteins. Here, we report the pathologic consequences of\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    deficiency in mice.\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice gain weight slowly, appear malnourished, and exhibit progressive hair loss. The most striking pathologic phenotype is multiple spontaneous bone fractures\u2014akin to those occurring in mouse models of osteogenesis imperfecta. Cortical and trabecular bone volumes are significantly reduced in\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice.\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice also manifested muscle weakness in the lower and upper extremities, resembling mice lacking the farnesylated\n                    <jats:italic>CAAX<\/jats:italic>\n                    protein prelamin A. Prelamin A processing was defective both in fibroblasts lacking\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    and in fibroblasts lacking the\n                    <jats:italic>CAAX<\/jats:italic>\n                    carboxyl methyltransferase Icmt but was normal in fibroblasts lacking the\n                    <jats:italic>CAAX<\/jats:italic>\n                    endoprotease Rce1. Muscle weakness in\n                    <jats:italic>Zmpste24<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice can be reasonably ascribed to defective processing of prelamin A, but the brittle bone phenotype suggests a broader role for Zmpste24 in mammalian biology.\n                  <\/jats:p>","DOI":"10.1073\/pnas.192460799","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T12:58:07Z","timestamp":1033477087000},"page":"13049-13054","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":416,"title":["<i>Zmpste24<\/i>\n                    deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect"],"prefix":"10.1073","volume":"99","author":[{"given":"Martin O.","family":"Bergo","sequence":"first","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryant","family":"Gavino","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jed","family":"Ross","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter K.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Hong","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lonnie V.","family":"Kendall","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Mohr","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Meta","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Genant","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yebin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik R.","family":"Wisner","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"van Bruggen","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A. D.","family":"Carano","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Michaelis","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Griffey","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen G.","family":"Young","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100; Cardiovascular Research Institute, University of California, San Francisco, CA 94143; Genentech, Incorporated, South San Francisco, CA 94080; Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Comparative Pathology Laboratory, University of California, Davis, CA 95616; Department of Radiology, University of California, San Francisco, CA 94143; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,9,16]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.2.271"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.142.3.635"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5307.1796"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/150.1.95"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb07694.x"},{"key":"e_1_3_3_6_2","first-page":"155","volume-title":"The Enzymes","author":"Young S G","year":"2000","unstructured":"S G Young, P Ambroziak, E Kim, S Clarke The Enzymes, eds F Tamanoi, D S Sigman (Academic, San Diego) 21, 155\u2013213 (2000)."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.01-10-0488"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065810"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102908200"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.8.5298"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81073-9"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng871"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1097-223"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.13.8383"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000831200"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116252"},{"key":"e_1_3_3_17_2","first-page":"5241","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Byers P H","year":"2001","unstructured":"P H Byers The Metabolic and Molecular Bases of Inherited Disease, eds C R Scriver, A L Beaudet, W S Sly, D Valle, B Childs, K W Kinzler, B Vogelstein (McGraw\u2013Hill, New York) 4, 5241\u20135285 (2001)."},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/332131a0"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.18.7145"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.53.37923"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0684.1996.tb00025.x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.147.5.913"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.13.8379"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00482-2"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1463"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.192460799","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T05:15:21Z","timestamp":1649826921000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.192460799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,9,16]]},"references-count":25,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2002,10]]}},"alternative-id":["10.1073\/pnas.192460799"],"URL":"https:\/\/doi.org\/10.1073\/pnas.192460799","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,9,16]]},"assertion":[{"value":"2002-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-08-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-09-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}