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 (PTENLoxp/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.
Highlights
The mouse stomach consists of squamous forestomach, glandular corpus and antrum
The three above-mentioned cells are believed to differentiate from stem cells of gastric isthmus and their dysfunction has been reported to be involved in atrophic gastritis and gastric cancers [1,2]
We generated a transgenic mouse strain (K19-Cre) in which Cre recombinase expression was under the control of a 2.8-kb promoter of the mouse cytokeratin 19 gene (K19)
Summary
The mouse stomach consists of squamous forestomach, glandular corpus and antrum. The gastric unit in the corpus region has pit cells, parietal cells, chief cells, mucous neck cells, stem cells, and enteroendocrine cells, whereas there are only mucus-producing pit and neck cells in gastric units of distal antrum. The mucusproducing pit cells are localized to the edge of the gastric mucosa. Parietal cells in oxyntic and cardiac glands secrete HCl by hydrogen potassium ATPase. Chief cells in oxyntic gland release pepsinogen, chymosin, lipase enzymes and leptin. The three above-mentioned cells are believed to differentiate from stem cells of gastric isthmus and their dysfunction has been reported to be involved in atrophic gastritis and gastric cancers [1,2]
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