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Existing <jats:italic>Runx2<\/jats:italic> mutant and transgenic mouse models do not allow the necessary control of <jats:italic>Runx2<\/jats:italic> expression to understand its functions in different tissues. We generated conditional, doxycyline\u2010inducible, triple transgenic mice (<jats:italic>CMV<\/jats:italic>\u2010Cre;<jats:italic>ROSA26<\/jats:italic>\u2010neo<jats:sup>flox\/+<\/jats:sup>\u2010rtTA;Tet\u2010O\u2010<jats:italic>Runx2<\/jats:italic>) to investigate the effects of wide spread overexpression of <jats:italic>Runx2<\/jats:italic>. Osteoblasts isolated from <jats:italic>CMV<\/jats:italic>\u2010Cre;<jats:italic>ROSA26\u2010<\/jats:italic>neo<jats:sup>flox\/+<\/jats:sup>\u2010rtTA; Tet\u2010O\u2010<jats:italic>Runx2<\/jats:italic> mice demonstrated a dose\u2010dependent effect of doxycycline to stimulate <jats:italic>Runx2<\/jats:italic> transgene expression. Doxycycline administration to <jats:italic>CMV<\/jats:italic>\u2010Cre;ROSA26<jats:italic>\u2010<\/jats:italic>neo<jats:sup>flox\/+<\/jats:sup>\u2010rtTA;Tet\u2010O\u2010<jats:italic>Runx2<\/jats:italic> mice induced <jats:italic>Runx2<\/jats:italic> transgene expression in all tissues tested, with the highest levels observed in kidney, ovary, and bone. Runx2 overexpression resulted in deceased body size and reduced viability. With regard to bone, <jats:italic>Runx2<\/jats:italic> overexpressing mice paradoxically displayed profound osteopenia and diminished osteogenesis. Induced expression of <jats:italic>Runx2<\/jats:italic> in extraskeletal tissues resulted in ectopic calcification and induction of the osteogenic program in a limited number of tissues, including lung and muscle. In addition, the triple transgenic mice showed evidence of a myeloproliferative disorder and an apparent inhibition of lymphocyte development. Thus, overexpression of <jats:italic>Runx2<\/jats:italic> both within and outside of the skeleton can have diverse biological effects. Use of tissue specific Cre mice will allow this model to be used to conditionally and inducibly overexpress <jats:italic>Runx2<\/jats:italic> in different tissues and provide a means to study the post\u2010natal tissue\u2010 and cell context\u2010dependent functions of Runx2. J. Cell. Biochem. 112: 653\u2013665, 2011. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.22968","type":"journal-article","created":{"date-parts":[[2010,12,6]],"date-time":"2010-12-06T14:01:32Z","timestamp":1291644092000},"page":"653-665","source":"Crossref","is-referenced-by-count":19,"title":["Inducible expression of <i>Runx2<\/i> results in multiorgan abnormalities in mice"],"prefix":"10.1002","volume":"112","author":[{"given":"Nan","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhousheng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Stubbs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. 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