TY - JOUR
T1 - Generation of transgenic mice for conditional overexpression of Sox9
AU - Kim, Youngwoo
AU - Murao, Hiroki
AU - Yamamoto, Koji
AU - Deng, Jian Min
AU - Behringer, Richard R.
AU - Nakamura, Takashi
AU - Akiyama, Haruhiko
N1 - Funding Information:
We thank Benoit de Crombrugghe, Philippe Soriano, Chisa Shukunami, and Roger Y. Tsien for valuable help. This work was supported by a grant-in-aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology no. 21249078 to H.A. and the National Institutes of Health HD30284 to R.R.B.
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - Col10a1
KW - Conditional expression
KW - Sox9
KW - Transgenic mouse
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U2 - 10.1007/s00774-010-0206-z
DO - 10.1007/s00774-010-0206-z
M3 - Article
C2 - 20676705
AN - SCOPUS:79951671983
SN - 0914-8779
VL - 29
SP - 123
EP - 129
JO - Journal of Bone and Mineral Metabolism
JF - Journal of Bone and Mineral Metabolism
IS - 1
ER -