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Induction of transgene expression in Tg.AC (v‐Ha‐ ras ) transgenic mice concomitant with DNA hypomethylation
Author(s) -
Can Ronald E.,
Spalding Judson W.,
Virgil Kelly M.,
Faircloth Randall S.,
Humble Michael C.,
Lacks Gregory D.,
Tennant Raymond W.
Publication year - 1998
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199804)21:4<244::aid-mc3>3.0.co;2-k
Subject(s) - transgene , biology , microbiology and biotechnology , southern blot , genetically modified mouse , complementary dna , gene , genetics
Tg.AC transgenic mice have a transgene composed of a ζ‐globin transcriptional control region, a v‐Ha‐ ras coding region, and a simian virus 40 3′ polyadenylation signal sequence. Induced ectopic expression of the transgene by chemical treatment or full‐skin‐thickness wounding leads to the development of skin papillomas. Reverse transcription–polymerase chain reaction assays and protein blotting indicated that the transgene was expressed 16–28 d after full‐skin‐thickness surgical wounding. Normal unwounded skin did not express the transgene. DNA blotting indicated that the position of the transgene remained stable during wound‐induced tumorigenesis. Concomitant with the v‐Ha‐ ras mRNA and protein expression was the hypomethylation of specific MspI/HpaII sites within the transgene. These results are consistent with the hypothesis that hypomethylation is required for the induced and sustained expression of the Tg.AC v‐Ha‐ ras transgene in spontaneous and induced tumors in Tg.AC mice. Mol. Carcinog. 21:244–250, 1998. © 1998 Wiley‐Liss, Inc.