Inducible expression of Runx2 results in multiorgan abnormalities in mice.
Inducible expression of Runx2 results in multiorgan abnormalities in mice.
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RUNX2的诱导表达导致小鼠多机构异常。
DOI：
10.1002/jcb.22968
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发表时间：
2011-02
影响因子：
4
通讯作者：
Quarles, L. Darryl
中科院分区：
文献类型：
--
作者：
He, Nan;Xiao, Zhousheng;Yin, Tong;Stubbs, Jason;Li, Linheng;Quarles, L. Darryl
Runx 2是一种控制骨骼发育的转录因子，也在其功能尚不清楚的骨骼外组织中表达。现有的Runx 2突变体和转基因小鼠模型不允许对Runx 2表达进行必要的控制以了解其在不同组织中的功能。我们产生了条件性的、多西环素诱导的三重转基因小鼠（CMV-Cre; ROSA 26-neoflox/+-rtTA;Tet-O-Runx 2）以研究Runx 2的广泛过表达的影响。从CMV-Cre; ROSA 26-neoflox/+-rtTA; Tet-O-Runx 2小鼠分离的成骨细胞证明了多西环素刺激Runx 2转基因表达的剂量依赖性作用。对CMV-Cre; ROSA 26-neoflox/+-rtTA;Tet-O-Runx 2小鼠施用多西环素在所有测试组织中诱导Runx 2转基因表达，在肾脏、卵巢和骨骼中观察到最高水平。Runx 2过度表达导致身体尺寸减小和生存能力降低。关于骨，Runx 2过表达小鼠矛盾地显示出严重的骨质减少和骨生成减少。Runx 2在皮肤外组织中的诱导表达导致异位钙化，并在有限数量的组织中诱导成骨程序，包括肺和肌肉。此外，三重转基因小鼠显示出骨髓增生性疾病和淋巴细胞发育明显抑制的证据。因此，Runx 2在骨骼内和骨骼外的过表达可以具有不同的生物学效应。使用组织特异性Cre小鼠将允许该模型用于在不同组织中有条件地和诱导地过表达Runx 2，并提供研究Runx 2的出生后组织和细胞环境依赖性功能的手段。
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.
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影响因子：
4.8
作者：
Byon, Chang Hyun;Javed, Amjad;Chen, Yabing
通讯作者：
Chen, Yabing
DOI：
10.1073/pnas.0409121102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Javed, A;Barnes, GL;Stein, GS
通讯作者：
Stein, GS
影响因子：
11.2
作者：
Blyth, K;Vaillant, F;Cameron, ER
通讯作者：
Cameron, ER
影响因子：
5.3
作者：
Geoffroy, V;Kneissel, M;Matthias, P
通讯作者：
Matthias, P
影响因子：
82.9
作者：
Ichikawa, M;Asai, T;Kurokawa, M
通讯作者：
Kurokawa, M