Use of a Transgenic Mouse Model With a Regulatable Estrogen Receptor Alpha (ER) to Study the Role of ER in Mammary Gland Development and Cancer
Final rept. 20 Aug 2001-19 Aug 2004
MEDICAL COLL OF WISCONSIN MILWAUKEE
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Estrogen E2 is required for the development of breast cancer, but there are few animal models to study its mechanism of action in vivo. We hypothesize that the timing of estrogen receptor alpha ERalpha action is crucial in normal mammary gland development and tumorigenesis. Therefore, a transgenic mouse model with a regulatable ERalpha is being generated. In vitro, a mutant ERalpha 525L has a severely attenuated response to endogenous estradiol E2 but a wild-type WT response to diethylstibestrol DES. Gene targeting was used to insert 525L into the WT ER gene. Positive clones were injected into mouse blastocysts and chimeras were generated. There has been no germline transmission so far. Additional injections and further breeding continues. The resultant transgenic mouse will enable us to study how the timing of ER activation modulates normal mammary maturation and the development of mammary cancers.
- Medicine and Medical Research