Cell-specific transgene expression from a widely transcribed promoter using Cre/lox in mice.
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 (TGFalpha), under control of the MT gene promoter. As long as DNA rearrangement does not occur in other cell types that express MT, TGFalpha expression will be restricted to acinar cells. Development of an effective target transgenic mouse required evaluation of multiple lineages to identify one with sufficient TGFalpha expression to induce pancreatic lesions after transgene rearrangement.
Grippo
Paul J
PJ
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53226, USA.
Nowlin
Patrick S
PS
Cassaday
Ryan D
RD
Sandgren
Eric P
EP
D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics; D015321:Gene Rearrangement; D019426:Integrases / Q000235:genetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D016366:Open Reading Frames; D010179:Pancreas / Q000378:metabolism; D010196:Pancreatic Elastase / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D016211:Transforming Growth Factor alpha / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; C081882:HpaP protein, Ralstonia solanacearum; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha; D014764:Viral Proteins; D008668:Metallothionein; C045073:Cre recombinase; D019426:Integrases; D001616:beta-Galactosidase; D010196:Pancreatic Elastase