The long range goal of this research is to use specifically tailored, regulable genetic construction to probe the molecular mechanisms responsible for, or related to, the control of early mammalian development, some types of birth defects and specific classes of infertility. The specific aims of this proposal, toward achievement of these long term goals, are (1) the development of methods for the high efficiency, stable, genetic transformation of laboratory mammals and (2) the construction and introduction of externally regulable genetic sequences into these animals. Specifically, the use of retroviral rectors and heteralogous transposition elements will be attempted to achieve high efficiency gene transfer into mouse fertilized eggs and the adult animals developing therefrom. Using these transposition rectors, genetic constructions with promoter/regulator sequences responsive to hormonal regulation will be introduced into and studied in transgenic mice.