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

摘要

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.