The development of appropriate animal models is an important step in the study of any human disease and the development of therapies. The advent of transgenic and stem cell technology has provided researchers with a powerful tool to study many human diseases. This proposal is aimed at the application of transgenic technology to the guinea pig, a species that has not been previously targeted for transgenics. Transgenic guinea pig models will serve as invaluable research tools for the study of reproduction, infertility, neural peptide function, shock, and stroke. Commercially, the production of novel transgenic guinea pigs could be offered as a service, however, this research will develop transgenic guinea pigs carrying a human alpha estrogen receptor minigene. A transgenic guinea pig over-expressing the human estrogen receptor would serve as a valuable research model in many areas.
The aim of this proposal is to characterize the expression pattern of the human ER gene and study its effect on the brain and reproductive organs of the guinea pig. Once characterized, the transgenic guinea pigs could be sold as research models to study the role of the estrogen receptor in tumorigenesis, the mechanism of tamoxifen resistance, reproductive aging, and estrogen's neuro protective effects.