A stringent dual control system overseeing transcription and activity of the Cre recombinase for the liver-specific conditional gene knock-out mouse model

Yu Wu^{a, b},
Yinghua He^b,
Hongyu Zhang^b,
Xinlan Dai^b,
Xiaoyu Zhou^b,
Jun Gu^b,
Guan Wang^b,
Jingde Zhu^{a, b
, ,}

a.
Fudan University School of Medicine, Shanghai 200032, China
b.
Cancer Epigenetics and Gene Therapy Program, The State-key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai 200032, China

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Corresponding author: E-mail address: zhujingde@shsci.org (Jingde Zhu)

摘要

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Abstract: Liver cancer is one of the most threatening diseases in Chinese population. Just like in other tissues, tumor initiation and development in liver involve multiple steps of genetic and epigenetic alterations with several unknown details. However, unlike in other tissues, a tissue specific inducible Cre recombinase system that allows temporal and spatial deletion of a target DNA fragment is still not available for in vivo functional gene annotation in hepatocytes. In our pursuit to establish such a mouse model, we designed a dual inducible Cre transgene system and tested it in cultured cells. By combining a CCAAT/enhancer binding protein β (C/EBP β) promoter derived Tet-off expression system and the estrogen receptor (ER) mediated functional control, we show a desirable profile of both hepatocyte-specificity and regulability of the Cre expression in a series of critical assessments in the cell culture system, which provides confidence in continuation of our ongoing pursuit in mouse.
- Cre/loxP /
- Tet-off /
- hepatocyte-specific /
- doxycycline /
- 4-OHT /
- C/EBP β

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