Generation of H11-albumin-rtTA Transgenic Mice: A Tool for Inducible Gene Expression in the Liver

• Published in: G3 : genes - genomes - genetics Vol. 9; no. 2; pp. 591 - 599
• Main Authors: Li, Yu-Shan, Meng, Ran-Ran, Chen, Xiu, Shang, Cui-Ling, Li, Hong-Bin, Zhang, Tao-Jun, Long, Hua-Yang, Li, Hui-Qi, Wang, Yi-Jing, Wang, Feng-Chao
• Format: Journal Article
• Language: English
• Published: United States Genetics Society of America 01.02.2019; Oxford University Press
• Subjects: albumin promoter; doxycycline; Hipp11; Investigations; Tet-on system; Hipp11; Tet-on system; albumin promoter; Doxycycline
• ISSN: 2160-1836; 2160-1836
• DOI: 10.1534/g3.118.200963

The modification of the mouse genome by site-specific gene insertion of transgenes and other genetic elements allows the study of gene function in different developmental stages and in the pathogenesis of diseases. Here, we generated a "genomic safe harbor" ( ) locus-specific knock-in transgenic mouse line in which the promoter is used to drive the expression of the reverse tetracycline transactivator (rtTA) in the liver. The newly generated transgenic mice were bred with ) mice to assess inducibility and tissue-specificity. Expression of the H2BGFP fusion protein was observed exclusively upon doxycycline (Dox) induction in the liver of double transgenic mice. To further analyze the ability of the Dox-inducible to implement conditional DNA recombination, transgenic mice were crossed with and mice to generate triple transgenic mice. We successfully confirmed that the Cre-mediated recombination efficiency was as strong in Dox-induced mice as in the control mice. Finally, to characterize the expression-inducing effects of Dox in - mice in detail, we examined GFP expression in embryos at different developmental stages and found that newly conceived embryos of Dox-treated pregnant female mice were expressing reporter GFP by E16.5. Our study demonstrates that these new transgenic mice are a powerful and efficient tool for the temporally and spatially conditional manipulation of gene expression in the liver, and illustrates how genetic crosses with these new mice enable the generation of complex multi-locus transgenic animals for mechanistic studies.