{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:50:36Z","timestamp":1785865836435,"version":"3.56.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"33","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,8,16]]},"abstract":"<jats:p>\n                    Degenerative joint disease, also known as osteoarthritis, is the most common joint disorder in human beings. The molecular mechanism underlying this disease is not fully understood. Here, we report that disruption of\n                    <jats:italic>mitogen-inducible gene 6<\/jats:italic>\n                    (\n                    <jats:italic>Mig-6<\/jats:italic>\n                    ) in mice by homologous recombination leads to early onset degenerative joint disease, which is revealed by simultaneous enlargement and deformity of multiple joints, degradation of articular cartilage, and the development of bony outgrowths or osteophyte formation within joint space. The osteophyte formation appears to be derived from proliferation of mesenchymal progenitor cells followed by differentiation into chondrocytes. Absence of the\n                    <jats:italic>Rag2<\/jats:italic>\n                    gene does not rescue the joint phenotype, excluding a role for the acquired immune system in the development of this disease. Our results provide insight into the mechanism of osteoarthritis by showing that loss of\n                    <jats:italic>Mig-6<\/jats:italic>\n                    leads to early onset of this disease, implying that this gene or its pathway is important in normal joint maintenance. Because of the striking similarity of osteoarthritis in humans and mice, the\n                    <jats:italic>Mig-6<\/jats:italic>\n                    mutant mouse should provide a useful animal model for studying the mechanism of this disease and for testing drugs or therapies for treating osteoarthritis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0505171102","type":"journal-article","created":{"date-parts":[[2005,8,8]],"date-time":"2005-08-08T20:33:51Z","timestamp":1123533231000},"page":"11740-11745","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":84,"title":["Targeted disruption of\n                    <i>Mig-6<\/i>\n                    in the mouse genome leads to early onset degenerative joint disease"],"prefix":"10.1073","volume":"102","author":[{"given":"Yu-Wen","family":"Zhang","sequence":"first","affiliation":[{"name":"Laboratories of Molecular Oncology and Germline Modification, Van Andel Research Institute, Grand Rapids, MI 49503; Department of Pathology, Harvard Medical School, Boston, MA 02115; Esperion Therapeutics, Ann Arbor, MI 48108; and Departments of Medicine and Rheumatology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49546"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Su","sequence":"additional","affiliation":[{"name":"Laboratories of Molecular Oncology and Germline Modification, Van Andel Research Institute, Grand Rapids, MI 49503; Department of Pathology, Harvard Medical School, Boston, MA 02115; Esperion Therapeutics, Ann Arbor, MI 48108; and Departments of Medicine and Rheumatology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49546"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Lanning","sequence":"additional","affiliation":[{"name":"Laboratories of Molecular Oncology and Germline Modification, Van Andel Research Institute, Grand Rapids, MI 49503; Department of Pathology, Harvard Medical School, Boston, MA 02115; Esperion Therapeutics, Ann Arbor, MI 48108; and Departments of Medicine and Rheumatology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49546"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela J.","family":"Swiatek","sequence":"additional","affiliation":[{"name":"Laboratories of Molecular Oncology and Germline Modification, Van Andel Research Institute, Grand Rapids, MI 49503; Department of Pathology, Harvard Medical School, Boston, MA 02115; Esperion Therapeutics, Ann Arbor, MI 48108; and Departments of Medicine and Rheumatology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49546"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick T.","family":"Bronson","sequence":"additional","affiliation":[{"name":"Laboratories of Molecular Oncology and Germline Modification, Van Andel Research Institute, Grand Rapids, MI 49503; Department of Pathology, Harvard Medical School, Boston, MA 02115; Esperion Therapeutics, Ann Arbor, MI 48108; and Departments of Medicine and Rheumatology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49546"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sigler","sequence":"additional","affiliation":[{"name":"Laboratories of Molecular Oncology and Germline Modification, Van Andel Research Institute, Grand Rapids, MI 49503; Department of Pathology, Harvard Medical School, Boston, MA 02115; Esperion Therapeutics, Ann Arbor, MI 48108; and Departments of Medicine and Rheumatology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49546"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.","family":"Martin","sequence":"additional","affiliation":[{"name":"Laboratories of Molecular Oncology and Germline Modification, Van Andel Research Institute, Grand Rapids, MI 49503; Department of Pathology, Harvard Medical School, Boston, MA 02115; Esperion Therapeutics, Ann Arbor, MI 48108; and Departments of Medicine and Rheumatology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49546"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George F.","family":"Vande Woude","sequence":"additional","affiliation":[{"name":"Laboratories of Molecular Oncology and Germline Modification, Van Andel Research Institute, Grand Rapids, MI 49503; Department of Pathology, Harvard Medical School, Boston, MA 02115; Esperion Therapeutics, Ann Arbor, MI 48108; and Departments of Medicine and Rheumatology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49546"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,8,8]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"427","volume":"16","year":"1989","unstructured":"Lawrence, R. 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B., Schoor, M., Chen, H., Marks, M. E., Harley, V., Mishina, Y. & Kingsley, D. M. 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