Epigenetic mechanisms affect mutant p53 transgene expression in WAP-mutp53 transgenic mice.

Details

Serval ID
serval:BIB_B436C23881B1
Type
Article: article from journal or magazin.
Collection
Publications
Title
Epigenetic mechanisms affect mutant p53 transgene expression in WAP-mutp53 transgenic mice.
Journal
Oncogene
Author(s)
Krepulat F., Löhler J., Heinlein C., Hermannstädter A., Tolstonog G.V., Deppert W.
ISSN
0950-9232 (Print)
ISSN-L
0950-9232
Publication state
Published
Issued date
07/07/2005
Peer-reviewed
Oui
Volume
24
Number
29
Pages
4645-4659
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
We describe the construction and phenotypic characterization of 23 whey acidic protein (WAP)-mutp53 transgenic mouse lines. The mutp53-expressing lines showed a mosaic expression pattern for the transgenes, leading to a heterogeneous yet mouse line-specific expression pattern for mutp53 upon induction. Only few lines were obtained, in which the majority of the induced mammary epithelial cells expressed the mutp53 transgene, most of the transgenic lines did not express mutp53, or expressed the transgene in less than 2% of the induced mammary epithelial cells. Hormone requirements for mutp53 transgene expression from the WAP-promoter differed in high and low expressing lines, being low in high expressing lines, and even lower in multiparous mutp53 mice, where persistent expression of the transgene occurred. Repeated induction of mutp53 expression through repeated parturition resulted in the formation of expanding mutp53-expressing foci within the mammary alveolar epithelium. The data suggest that epigenetic mechanisms play a role in modulating the expression of the mutp53 transgene. To support this idea, we crossed a nonexpressing WAP-mutp53 line with a strongly SV40 T-antigen-expressing WAP-T mouse line. In the bitransgenic mice, T-antigen-induced chromatin remodeling led to re-expression of epigenetically silenced mutp53 transgene(s). In these mice, mutp53 expression was much more variable compared to SV40 T-antigen expression, and seemed to depend on the coexpression of SV40 T-antigen. Mutp53 expression in this system thus resembles the situation in many human tumors, where one can observe a heterogeneous expression of mutp53, despite a homogeneous distribution of the p53 mutation in the tumor cells.
Keywords
Animals, Cell Line, Disease Models, Animal, Epigenesis, Genetic, Female, Gene Expression Regulation, Genes, p53, Male, Mice, Mice, Transgenic, Milk Proteins/genetics, Mosaicism, Mutation, Phenotype, Transgenes
Pubmed
Web of science
Open Access
Yes
Create date
15/12/2017 16:19
Last modification date
14/01/2020 6:26
Usage data