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Cell-specific transgene expression from a widely transcribed promoter using Cre/lox in mice
Paul J Grippo1, Patrick S Nowlin, Ryan D Cassaday
1Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53226, USA.
Genesis (New York, N.Y. : 2000)
|April 12, 2002
Summary
Researchers developed a novel transgenic mouse model for studying pancreatic cancer. This system ensures sustained, tissue-specific expression of transforming growth factor alpha (TGFalpha) during tumor development, overcoming previous limitations in transgene expression.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Evaluating oncogene interactions in carcinogenesis often uses multi-transgenic mice.
- Neoplastic transformation typically reduces expression of differentiation-specific genes and transgenes.
- Metallothionein (MT) gene expression remains high in some neoplasms, including pancreatic ones.
Purpose of the Study:
- To develop a system for sustained, tissue-specific transgene expression during pancreatic carcinogenesis.
- To overcome the challenge of reduced transgene expression during neoplastic transformation.
- To create a reliable transgenic mouse model for studying pancreatic cancer development.
Main Methods:
- Utilized Cre recombinase and a lox site-containing target transgene.
- Expressed Cre in pancreatic acinar cells under the elastase promoter (EL).
- Achieved Cre-mediated recombination to place rat transforming growth factor alpha (TGFalpha) under the MT gene promoter.
Main Results:
- Developed a system maintaining high-level, tissue-specific transgene expression in pancreatic neoplasms.
- TGFalpha expression was restricted to acinar cells, contingent on no other MT-expressing cell DNA rearrangement.
- Identified effective target transgenic lineages with sufficient TGFalpha expression to induce pancreatic lesions.
Conclusions:
- The developed system enables sustained, acinar cell-specific TGFalpha expression during pancreatic carcinogenesis.
- This model overcomes limitations of reduced transgene expression in neoplastic transformation.
- The system is crucial for evaluating oncogene interactions and developing therapeutic strategies for pancreatic cancer.