Inducible expression of Runx2 results in multiorgan abnormalities in mice

Nan He, Zhousheng Xiao, Tong Yin, Jason Stubbs, Linheng Li, Leigh Quarles

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Runx2 is a transcription factor controlling skeletal development, and is also expressed in extraskeletal tissues where its function is not well understood. Existing Runx2 mutant and transgenic mouse models do not allow the necessary control of Runx2 expression to understand its functions in different tissues. We generated conditional, doxycyline-inducible, triple transgenic mice (CMV-Cre;ROSA26-neoflox/+-rtTA;Tet-O-Runx2) to investigate the effects of wide spread overexpression of Runx2. Osteoblasts isolated from CMV-Cre;ROSA26-neoflox/+-rtTA; Tet-O-Runx2 mice demonstrated a dose-dependent effect of doxycycline to stimulate Runx2 transgene expression. Doxycycline administration to CMV-Cre;ROSA26-neoflox/+-rtTA;Tet-O- Runx2 mice induced Runx2 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, Runx2 overexpressing mice paradoxically displayed profound osteopenia and diminished osteogenesis. Induced expression of Runx2 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 Runx2 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 Runx2 in different tissues and provide a means to study the post-natal tissue- and cell context-dependent functions of Runx2.

Original languageEnglish (US)
Pages (from-to)653-665
Number of pages13
JournalJournal of Cellular Biochemistry
Volume112
Issue number2
DOIs
StatePublished - Feb 1 2011

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Tissue
Transgenic Mice
Doxycycline
Transgenes
Bone
Bone and Bones
Myeloproliferative Disorders
Lymphocytes
Metabolic Bone Diseases
Osteoblasts
Body Size
Osteogenesis
Skeleton
Muscle
Ovary
Transcription Factors
Kidney
Muscles
Lung

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Inducible expression of Runx2 results in multiorgan abnormalities in mice. / He, Nan; Xiao, Zhousheng; Yin, Tong; Stubbs, Jason; Li, Linheng; Quarles, Leigh.

In: Journal of Cellular Biochemistry, Vol. 112, No. 2, 01.02.2011, p. 653-665.

Research output: Contribution to journalArticle

He, Nan ; Xiao, Zhousheng ; Yin, Tong ; Stubbs, Jason ; Li, Linheng ; Quarles, Leigh. / Inducible expression of Runx2 results in multiorgan abnormalities in mice. In: Journal of Cellular Biochemistry. 2011 ; Vol. 112, No. 2. pp. 653-665.
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