{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:02:20Z","timestamp":1791028940558,"version":"4.1.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[1995,12,1]],"date-time":"1995-12-01T00:00:00Z","timestamp":817776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"NIH","award":["AR38188"],"award-info":[{"award-number":["AR38188"]}]},{"DOI":"10.13039\/100011517","name":"Lucille P. Markey Charitable Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011517","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1995,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>An inbred strain of transgenic mice that expressed a mutated gene for type I procollagen and that developed spontaneous fractures was used to study the effects of age on the phenotype of fragile bones. The mutated gene has been shown to cause depletion of type I collagen in the transgenic mice because it generated shortened pro\u03b11(I) chains that bound to and produced degradation of normal pro\u03b11(I) chains synthesized from the endogenous mouse COL1A1 gene. For this study, femurs from transgenic mice ranging in age from 0.5\u201324 months were examined. The results demonstrated that the level of expression of the transgene was independent of age. Femurs from the transgenic mice were more fragile than controls at 0.5 and 1.5 months, they were biomechanically normal at 6 months, and then they were more fragile at 24 months. The normal biomechanical properties of the bones from the transgenic mice at 6 months were accompanied by periosteal thickening of the bones together with an increase in the collagen content that was not associated with a proportional increase in mineral content. The results indicated that the effects of age, mechanical stress, and hormonal action produced a biological compensation for the mutated gene by either increasing collagen synthesis of bone, decreasing collagen degradation, or both. The biological compensation was apparently lost by 24 months when the outer diameters of the femurs were again less than in controls, the cortical thickness was about the same as in controls, and both the collagen and mineral contents were less than controls. The results demonstrated that bone fragility in the transgenic mice paralleled the age-dependent phenotype of human osteogenesis imperfecta. Therefore the transgenic mice appeared to be useful models for osteogenesis imperfecta. They also may be useful models for some forms of osteoporosis.<\/jats:p>","DOI":"10.1002\/jbmr.5650101202","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T16:02:57Z","timestamp":1265212977000},"page":"1837-1843","source":"Crossref","is-referenced-by-count":41,"title":["Bone fragility in transgenic mice expressing a mutated gene for type I procollagen (COL1A1) parallels the age-dependent phenotype of human osteogenesis imperfecta"],"prefix":"10.1093","volume":"10","author":[{"given":"Ruth F.","family":"Pereira","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Jefferson Institute of Molecular Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric L.","family":"Hume","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Halford","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Jefferson Institute of Molecular Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darwin J.","family":"Prockop","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Jefferson Institute of Molecular Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1995,12,1]]},"reference":[{"key":"2024013113140969700_bib1","first-page":"2105","volume-title":"Harrison's Principles of Internal Medicine","author":"Prockop","year":"1994","edition":"13th Ed"},{"key":"2024013113140969700_bib2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev.med.45.1.149","article-title":"Molecular basis of hereditary disorders of connective tissues","volume":"45","author":"Tilstra","year":"1994","journal-title":"Ann Rev Med"},{"key":"2024013113140969700_bib3","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1002\/jbmr.5650090618","article-title":"Mutation analysis of coding sequences for type I procollagen in individuals with low bone density","volume":"9","author":"Spotila","year":"1994","journal-title":"J Bone Miner Res"},{"key":"2024013113140969700_bib4","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/0092-8674(84)90514-2","article-title":"Embryonic lethal mutation in mouse collagen I gene causes rupture of blood vessels and is associated with erythropoietic and mesenchymal cell death","volume":"38","author":"Lohler","year":"1984","journal-title":"Cell"},{"key":"2024013113140969700_bib5","doi-asserted-by":"crossref","first-page":"7145","DOI":"10.1073\/pnas.87.18.7145","article-title":"A transgenic mouse model of osteogenesis imperfecta type I","volume":"87","author":"Bonadio","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013113140969700_bib6","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1172\/JCI116756","article-title":"A murine skeletal adaptation that significantly increases cortical bone mechanical properties","volume":"92","author":"Bonadio","year":"1993","journal-title":"J Clin Invest"},{"key":"2024013113140969700_bib7","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1073\/pnas.90.5.1701","article-title":"Defective pro\u03b12(I) collagen synthesis in a recessive mutation in mice: a model of osteogenesis imperfecta","volume":"90","author":"Chipman","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013113140969700_bib8","doi-asserted-by":"crossref","first-page":"23373","DOI":"10.1016\/S0021-9258(18)54506-3","article-title":"Transgenic mice that express a mini-gene version of the human gene for type I procollagen (COL1A1) develop a phenotype resembling a lethal form of osteogenesis imperfecta","volume":"266","author":"Khillan","year":"1991","journal-title":"J Biol Chem"},{"key":"2024013113140969700_bib9","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1172\/JCI116252","article-title":"Transgenic mice expressing a partially deleted gene for type I procollagen (COL1A1). A breeding line with a phenotype of spontaneous fractures and decreased bone collagen and mineral","volume":"91","author":"Pereira","year":"1993","journal-title":"J Clin Invest"},{"key":"2024013113140969700_bib10","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1172\/JCI117161","article-title":"Phenotypic variability and incomplete penetrance of spontaneous fractures in an inbred strain of transgenic mice expressing a mutated collagen gene (COL1A1)","volume":"93","author":"Pereira","year":"1994","journal-title":"J Clin Invest"},{"key":"2024013113140969700_bib11","doi-asserted-by":"crossref","first-page":"9242","DOI":"10.1021\/bi00086a033","article-title":"Tissue- and development-specific expression in transgenic mice in the type I procollagen (COL1A1) mini-gene construct with 2.3 kb of the promoter region and 2 kb of the 3\u2032-flanking region. Specificity is independent of putative regulatory sequences of the first intron","volume":"32","author":"Sokolov","year":"1993","journal-title":"Biochemistry"},{"key":"2024013113140969700_bib12","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/8756-3282(94)90308-5","article-title":"An ultrastructural, microanalytical, and spectroscopic study of bone from a transgenic mouse with a COL1.A1 pro-alpha-1 mutation","volume":"15","author":"Cassella","year":"1994","journal-title":"Bone"},{"key":"2024013113140969700_bib13","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1006\/abio.1987.9999","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomzynski","year":"1987","journal-title":"Anal Biochem"},{"key":"2024013113140969700_bib14","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/0003-9861(61)90291-0","article-title":"The determination of hydroxyproline in tissue and protein sample containing small proportions of this amino acid","volume":"93","author":"Woessner","year":"1961","journal-title":"Arch Biochem Biophys"},{"key":"2024013113140969700_bib15","doi-asserted-by":"crossref","first-page":"9181","DOI":"10.1016\/S0021-9258(18)34258-3","article-title":"Structure and helical stability of a modified procollagen synthesized in the presence of 3,4-dehydroproline. A decrease in amino acid content suggesting that the analog increases the error rate of translation of proline codons","volume":"257","author":"Fiedler-Nagy","year":"1982","journal-title":"J Biol Chem"},{"key":"2024013113140969700_bib16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/jbmr.5650030107","article-title":"Bone status of senescent male rats: chemical, morphometric, and mechanical analysis","volume":"3","author":"Kiebzak","year":"1988","journal-title":"J Bone Miner Res"},{"key":"2024013113140969700_bib17","first-page":"1","volume-title":"The Osteoporotic Syndrome: Detection, Prevention, and Treatment","author":"Pacifici","year":"1993","edition":"3rd Ed"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.5650101202","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/10\/12\/1837\/56498591\/5650101202.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/10\/12\/1837\/56498591\/5650101202.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:01:33Z","timestamp":1710342093000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/10\/12\/1837-1843\/7500741"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,12,1]]},"references-count":17,"journal-issue":{"issue":"12","published-online":{"date-parts":[[1995,12,1]]},"published-print":{"date-parts":[[1995,12,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.5650101202","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1995,12,1]]},"published":{"date-parts":[[1995,12,1]]}}}