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Cell‐specific transgene expression from a widely transcribed promoter using Cre/ lox in mice
Author(s) -
Grippo Paul J.,
Nowlin Patrick S.,
Cassaday Ryan D.,
Sandgren Eric P.
Publication year - 2002
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.10080
Subject(s) - transgene , biology , cre recombinase , carcinogenesis , microbiology and biotechnology , gene , promoter , genetically modified mouse , gene expression , genetics
Summary: Mice carrying two or more transgenes are used frequently to evaluate oncogene interactions during carcinogenesis. However, neoplastic transformation typically results in reduced expression both of differentiation‐specific genes and of transgenes that use their promoters. In contrast, the more widely expressed metallothionein (MT) gene remains expressed at a high level in certain neoplasms, including those developing in pancreas. We have developed a system to maintain high‐level, tissue‐specific transgene expression during pancreatic carcinogenesis that uses Cre recombinase and a lox site‐containing target transgene. Cre was expressed in pancreatic acinar cells under control of the elastase promoter (EL). Cre‐mediated target transgene recombination placed a previously silent open‐reading frame, encoding rat transforming growth factor alpha (TGFα), under control of the MT gene promoter. As long as DNA rearrangement does not occur in other cell types that express MT, TGFα expression will be restricted to acinar cells. Development of an effective target transgenic mouse required evaluation of multiple lineages to identify one with sufficient TGFα expression to induce pancreatic lesions after transgene rearrangement. genesis 32:277–286, 2002. © 2002 Wiley‐Liss, Inc.