Generation of transgenic mice for conditional overexpression of Sox9.

Generation of transgenic mice for conditional overexpression of Sox9.
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DOI:
10.1007/s00774-010-0206-z
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发表时间:
2011-01
影响因子:
3.3
通讯作者:
Akiyama, Haruhiko
Akiyama, Haruhiko
中科院分区:
医学3区
文献类型:
--
作者:
Kim, Youngwoo;Murao, Hiroki;Yamamoto, Koji;Deng, Jian Min;Behringer, Richard R.;Nakamura, Takashi;Akiyama, Haruhiko

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Sox 9属于Sry相关的高迁移率族盒转录因子家族,其控制各种组织中的细胞命运、细胞增殖和分化,包括软骨、睾丸、中枢神经系统、肾脏和胃肠。条件性缺乏Sox 9的小鼠已经揭示了Sox 9在这些组织中的重要作用。为了进一步了解Sox 9在不同组织和不同发育阶段的作用,我们已经产生了一个转基因小鼠系,以Cre重组酶依赖的方式表达Sox 9。该构建体含有人巨细胞病毒增强子和鸡β-肌动蛋白启动子,以及一个floxed单体红色荧光蛋白1(mRFP 1)盒,用于指导mRFP 1的普遍表达。Cre表达去除了mRFP 1基因,允许表达Sox 9和增强的绿色荧光蛋白。预期,使用Col 2a 1-Cre小鼠在软骨细胞中过表达Sox 9抑制软骨细胞肥大,并延迟终末分化和随后的骨化。Sox 9在肥大软骨细胞中的错误表达,使用Col 10a 1-Cre敲入小鼠也延迟了终末分化。这种Sox 9条件转基因小鼠系将是一个有价值的工具,揭示组织特异性和发育阶段特异性的功能Sox 9。
Sox9 belongs to the family of Sry-related high-mobility group box transcription factors controlling cell fate, cell proliferation and differentiation in various tissues, including cartilage, testis, the central nervous system, kidney, and gastrointestine. Mice conditionally lacking Sox9 have revealed essential roles for Sox9 in these tissues. To gain further insight into the role of Sox9 in different tissues and at different stages of development, we have generated a transgenic mouse line to express Sox9 in a Cre recombinase-dependent manner. The construct contained the human cytomegalovirus enhancer and chicken β-actin promoter, and a floxed monomeric red fluorescence protein 1 (mRFP1) cassette to direct ubiquitous expression of mRFP1. Cre expression removed the mRFP1 gene, allowing expression of Sox9 and enhanced green fluorescent protein. Expectedly, overexpression of Sox9 in chondrocytes using Col2a1-Cre mice suppressed chondrocyte hypertrophy, and delayed terminal differentiation and subsequent ossification. Misexpression of Sox9 in hypertrophic chondrocytes using Col10a1-Cre knock-in mice also delayed terminal differentiation. This Sox9 conditional transgenic mouse line will be a valuable tool to uncover tissue-specific and developmental stage-specific functions of Sox9.
DOI: 10.1101/gad.1017802
发表时间: 2002-11-01
影响因子: 10.5
作者:
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发表时间: 2007-05-01
期刊: MATRIX BIOLOGY
影响因子: 6.9
作者:
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