We have been successful in the last few years in introducing new genes into the germ line of mice. A significant number of these new genes have been expressed in the animals and their progeny. The present study involves the introduction of onc genes into mice. Many of the studies will be done with the SV40 early region which contains the large T and small t antigen genes. We have found this region will induce choroid plexus adenomas and carcinomas in transgenic mice. The genes are also expressed in other tissues of the animal. This provides a novel and exciting model in which to study the mechanism of oncogenesis. We wish to investigate the: (1) events associated with activation of the gene (e.g., DNA methylation, amplification, rearrangement); (2) role of the large T and small t coding sequences in tumor development; (3) role of enhancer elements in the frequency and target cell specificity of tumor development; (4) effects of other onc genes, such as src and ras; and (5) effect of carcinogenic agents on transgenic mice that contain onc genes but do not show obvious signs of malignancy. The ability to introduce known oncogenic DNA sequences into an animal and study the effect of the genes provides an excellent experimental system for studying cancer. The experiments in animals are particularly important for the identification of DNA changes associated in vivo with gene activation and factors controlling tissue-specific expression. (X)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038635-04
Application #
3176740
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1985-01-01
Project End
1989-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Sandgren, E P; Schroeder, J A; Qui, T H et al. (1995) Inhibition of mammary gland involution is associated with transforming growth factor alpha but not c-myc-induced tumorigenesis in transgenic mice. Cancer Res 55:3915-27
Rhim, J A; Sandgren, E P; Palmiter, R D et al. (1995) Complete reconstitution of mouse liver with xenogeneic hepatocytes. Proc Natl Acad Sci U S A 92:4942-6
Quaife, C J; Hoyle, G W; Froelick, G J et al. (1994) Visualization and ablation of phenylethanolamine N-methyltransferase producing cells in transgenic mice. Transgenic Res 3:388-400
Hammang, J P; Behringer, R R; Baetge, E E et al. (1993) Oncogene expression in retinal horizontal cells of transgenic mice results in a cascade of neurodegeneration. Neuron 10:1197-209
Cullen, J M; Sandgren, E P; Brinster, R L et al. (1993) Histologic characterization of hepatic carcinogenesis in transgenic mice expressing SV40 T-antigens. Vet Pathol 30:111-8
Luetteke, N C; Lee, D C; Palmiter, R D et al. (1993) Regulation of fat and muscle development by transforming growth factor alpha in transgenic mice and in cultured cells. Cell Growth Differ 4:203-13
Sandgren, E P; Luetteke, N C; Qiu, T H et al. (1993) Transforming growth factor alpha dramatically enhances oncogene-induced carcinogenesis in transgenic mouse pancreas and liver. Mol Cell Biol 13:320-30
Sandgren, E P; Palmiter, R D; Heckel, J L et al. (1992) DNA rearrangement causes hepatocarcinogenesis in albumin-plasminogen activator transgenic mice. Proc Natl Acad Sci U S A 89:11523-7
Messing, A; Behringer, R R; Hammang, J P et al. (1992) P0 promoter directs expression of reporter and toxin genes to Schwann cells of transgenic mice. Neuron 8:507-20
Gibson, C W; Lally, E; Herold, R C et al. (1992) Odontogenic tumors in mice carrying albumin-myc and albumin-rats transgenes. Calcif Tissue Int 51:162-7

Showing the most recent 10 out of 31 publications