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Induction of transgene expression in Tg.AC (v-Ha-ras) transgenic mice concomitant with DNA hypomethylation

✍ Scribed by Ronald E. Cannon; Judson W. Spalding; Kelly M. Virgil; Randall S. Faircloth; Michael C. Humble; Gregory D. Lacks; Raymond W. Tennant

Publisher
John Wiley and Sons
Year
1998
Tongue
English
Weight
289 KB
Volume
21
Category
Article
ISSN
0899-1987

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✦ Synopsis

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.

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