Characterization of a BAC transgenic mouse expressing Krt19-driven iCre recombinase in its digestive organs

• Published in: PloS one 2019-08, Vol.14 (8), p.e0220818-e0220818
• Main Authors: Kanayama, Tomohiro, Tomita, Hiroyuki, Binh, Nguyen Huy, Hatano, Yuichiro, Aoki, Hitomi, Okada, Hideshi, Hirata, Akihiro, Fujihara, Yoshitaka, Kunisada, Takahiro, Hara, Akira
• Format: Article
• Language: English
• Subjects: Animal genetic engineering; Animals; Artificial chromosomes; Bacterial artificial chromosomes; Bile; Biology and Life Sciences; Cells (Biology); Chromosomes; Chromosomes, Artificial, Bacterial - genetics; Cloning; Cytokeratin; Cytoskeletal proteins; Deoxyribonucleic acid; Digestive System - metabolism; DNA; Elderly; Embryos; Epithelial cells; Epithelium; Galactosidase; Gastrointestinal system; Gastrointestinal tract; Gene expression; Genes; Genes, Reporter; Genetic aspects; Genetic engineering; Genetic research; Genomes; Geriatrics; Health aspects; Integrases - metabolism; Journalists; Keratin; Keratin-19 - metabolism; Laboratory animals; Lac Operon; Mammalian cells; Medical research; Medicine; Medicine and Health Sciences; Methods; Mice; Mice, Transgenic - metabolism; Models, Animal; Neomycin; Newborn infants; Organs; Pancreas; Pathology; Proteins; Recombinase; Recombinases; Research and Analysis Methods; Rodents; Structure; Tissues; Tomatoes; Transgenic animals; Transgenic mice; Tumors; University graduates; β-Galactosidase
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0220818

Cytokeratin 19 (KRT19) protein is highly expressed in the epithelium of the gastrointestinal (GI) tract, hepatobiliary tissues, and pancreas of humans and mice. In the present study, we used an improved Cre (iCre) gene to enhance the efficiency of Cre expression in mammalian cells. We established a new transgenic Krt19-iCre bacterial artificial chromosome (BAC) mouse model using the BAC recombineering strategy. Site-specific iCre expression pattern was examined in embryos, adults, and elderly Krt19-iCre mice crossed with Tomato or LacZ reporter mice. Both iCre and reporter protein expressions in adult Krt19-iCre;Tomatoflox/+ (Krt19-iCre Tomato reporter) mice were observed mainly in the epithelial cells of the GI tract, hepatobiliary tissues, and pancreas. However, the expression in the intrahepatic and small pancreatic duct were lower than those in the common bile and large pancreatic duct. In the Krt19-iCre; LacZ reporter embryos, β-galactosidase for the LacZ reporter was expressed in the glandular epithelial cells of the GI tract in 9.5-day embryos, 12-day embryos, and newborn mice. The reporter protein expression in Krt19-iCre-Tomato reporter mice was consistent with the KRT19 expression in human GI tissues. In conclusion, Krt19-iCre BAC transgenic mice can be used to investigate developmental and pathological conditions using the iCre-loxP system.