{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:25:18Z","timestamp":1790630718195,"version":"4.1.0"},"reference-count":26,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,1,5]]},"abstract":"<jats:p>In vitro, ligand occupancy of \u03b1v\u03b23 integrin induces phosphorylation of Dap12, which is essential for osteoclast function. Like mice deleted of only \u03b1v\u03b23, Dap12\u2212\/\u2212 mice exhibited a slight increase in bone mass, but Dap12\u2212\/\u2212 mice, lacking another ITAM protein, FcR\u03b3, were severely osteopetrotic. The mechanism by which FcR\u03b3 compensates for Dap12 deficiency is unknown. We find that co-deletion of FcR\u03b3 did not exacerbate the skeletal phenotype of \u03b23\u2212\/\u2212 mice. In contrast, \u03b23\/Dap12 double-deficient (DAP\/\u03b23\u2212\/\u2212) mice (but not \u03b21\/Dap12 double-deficient mice) were profoundly osteopetrotic, reflecting severe osteoclast dysfunction relative to those lacking \u03b1v\u03b23 or Dap12 alone. Activation of OSCAR, the FcR\u03b3 co-receptor, rescued Dap12\u2212\/\u2212 but not DAP\/\u03b23\u2212\/\u2212osteoclasts. Thus, the absence of \u03b1v\u03b23 precluded compensation for Dap12 deficiency by FcR\u03b3. In keeping with this, Syk phosphorylation did not occur in OSCAR-activated DAP\/\u03b23\u2212\/\u2212 osteoclasts. Thus, FcR\u03b3 requires the osteoclast \u03b1v\u03b23 integrin to normalize the Dap12-deficient skeleton.<\/jats:p>","DOI":"10.1083\/jcb.201410123","type":"journal-article","created":{"date-parts":[[2014,12,30]],"date-time":"2014-12-30T08:03:49Z","timestamp":1419926629000},"page":"125-136","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":53,"title":["Absence of Dap12 and the \u03b1v\u03b23 integrin causes severe osteopetrosis"],"prefix":"10.1083","volume":"208","author":[{"given":"Wei","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology 1 , and 2"},{"name":"Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110 1 , and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Teitelbaum","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology 1 , and 2"},{"name":"Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110 1 , and 2"},{"name":"Department of Pathology and Immunology 1 , and 2"},{"name":"Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110 1 , and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2014,12,29]]},"reference":[{"key":"2023072307045471800_bib1","doi-asserted-by":"publisher","first-page":"3505","DOI":"10.1172\/JCI45913","article-title":"OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice","volume":"121","author":"Barrow","year":"2011","journal-title":"J. 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