SGER: Development of a Mouse With Inducible Estrogen Receptor Alpha Function

University Of Virginia Main Campus, Charlottesville VA

Investigators

Abstract

Estrogen is a steroid hormone that is important throughout the lifespan. It is involved in functions including cell migration, bone development, reproductive development, neurogenesis, heart function and even neural plasticity and cognition, as well as its well-known actions as a reproductive hormone. Estrogen acts at the cellular level through two main known molecular receptors, alpha (ER-a) and beta (ER-B). These receptors are transcription factors that promote cell growth and proliferation. The ER-a receptor is known from studies on genetic knockout (KO) mice to be the major receptor involved in reproductive social behaviors, and in non-reproductive behaviors such as exploratory behavior, learning and memory, as well has having an important function in development. This SGER project uses a novel approach to create an 'inducible' genetic KO mouse strain, rather than the simple knockouts currently available. The concept of an inducible knockout is not new, but there has been no reversible knockout developed for any of the steroid receptors, which have such widespread distribution and functional importance in the brain. The inducible genetic expression of ER-a will allow this steroid receptor function to be manipulated reversibly, and so turn the gene expression not only off, but also on again, during different stages of development and in adults, allowing exploration of whether there are distinct 'critical periods' in life for the function of this important receptor. This is a high-impact/high-risk project because the outcome is not clear, but the potential impact of success is wide-ranging. If successful, the results will lead to further studies on time-dependent functions of steroid hormones, and will have a high impact extending beyond neuroendocrinology into the areas such as developmental biology and cognitive neuroscience. The project also provides a valuable training experience for a graduate student bridging molecular biology with neuroendocrinology.