Tg(MMTV-rtTA)1Lach

The transgene comprises a 2.9-kb DNA fragment containing the MMTV LTR, 1.2 kb of LTR-upstream sequence, and 0.6 kb of v-Hras leader sequence; a 1.0-kb fragment containing a minigene encoding full-length reverse tetracycline transactivator (rtTA: "Tet-On"); and a 1.8 kb fragment containing the splicing and polyadenylation signals from SV40. Northern blot analysis readily detected rtTA transcripts in total mammary gland RNA from 5 week-old, doxycycline-treated, female transgenic mice. Upon induction by doxycycline, this transgene promoted high-level, homogeneous, reversible expression of beta-galactosidase or luciferase reporter transgenes in mammary epithelium, including terminal end buds, of female mice of various ages and reproductive states; expression was higher in pregnant and lactating mice than in virgin or post-involutional females. Except in older females continuously induced for at least 10 weeks, mammary glands of these mice were morphologically and functionally normal. rtTA and/or reporter expression was observed at lower levels in salivary gland, seminal vesicle and thymus, again only upon doxycycline administration. Older (15 weeks) induced bitrangenic female mice expressed beta-galactosidase in only 15-20% of mammary epithelial cells; however, levels of rtTA mRNA were only slightly lower than in 5 week-old induced mice. (J:75048)