Cytokeratin 19 promoter directs the expression of Cre recombinase in various epithelia of transgenic mice

Autor: Shuang Zhao, Zhi-Jie Li, Hua-Chuan Zheng, Gui-Feng Zhao, Xiao-Qing Ding, Xue-Wen Yu, Ke-Qiang Huang, Hao-Yu He, Jia-Jie Liu, Ji-Cheng Wu
Rok vydání: 2017
Předmět:
Zdroj: Oncotarget
ISSN: 1949-2553
DOI: 10.18632/oncotarget.15435
Popis: // Gui-Feng Zhao 1 , Shuang Zhao 1 , Jia-Jie Liu 1 , Ji-Cheng Wu 1 , Hao-Yu He 1 , Xiao-Qing Ding 1 , Xue-Wen Yu 2 , Ke-Qiang Huang 2 , Zhi-Jie Li 1 , Hua-Chuan Zheng 1 1 Department of Experimental Oncology and Animal Center, Shengjing Hospital of China Medical University, Shenyang 110004, China 2 Office of Administration, Jinzhou Medical University, Jinzhou 121001, China Correspondence to: Hua-Chuan Zheng, email: zheng_huachuan@hotmail.com Keywords: Cre recombinase, transgenic mouse, cytokeratin 19, PTEN, carcinogenesis Received: December 01, 2016 Accepted: January 11, 2017 Published: February 17, 2017 ABSTRACT Cytokeratin 19 (K19) is expressed in various differentiated cells, including gastric, intestinal and bronchial epithelial cells, and liver duct cells. Here, we generated a transgenic mouse line, K19-Cre, in which the expression of Cre recombinase was controlled by the promoter of K19. To test the tissue distribution and excision activity of Cre recombinase, K19-Cre transgenic mice were bred with Rosa26 reporter strain and a mouse strain that carries PTEN conditional alleles (PTEN Loxp/Loxp ). At mRNA level, Cre was strongly expressed in the stomach, lung and intestine, while in stomach, lung, and liver at protein level. The immunoreactivity to Cre was strongly observed the cytoplasm of gastric, bronchial and intestinal epithelial cells. Cre activity was detectable in gastric, bronchial and intestinal epithelial cells, according to LacZ staining. In K19-Cre/PTEN Loxp/Loxp mice, PTEN was abrogated in stomach, intestine, lung, liver and breast, the former two of which were verified by in situ PCR. There appeared breast cancer with PTEN loss. These data suggest that K19 promoter may be a useful tool to study the pathophysiological functions of cytokeratin 19-positive cells, especially gastrointestinal epithelial cells. Cell specificity of neoplasia is not completely attributable to the cell-specific expression of oncogenes and cell-specific loss of tumor suppressor genes.
Databáze: OpenAIRE