Thesis Seminar: Di Xu
An Old Gene Takes On a New Form: Expression and Functions of Renin Isoforms: Di Xu 11.February (Thursday) at 3:00pm in 2117 MERF
Hypertension is a complex disorder that could be a result of genetic defects (for example, interference with the Renin-angiotensin System), or contribution from environmental factors. Reninis the rate-limiting enzyme in the Renin-angiotensin System that modulates blood pressure. The classic renin protein is primarily synthesized and secreted from the kidney. Our lab and others have identified a novel isoform of renin that remains intracellular and mostly expressed in the brain, initially from transgenic animal studies. My thesis project aims to distinguish the difference between the secreted renin (sRen) and the intracellular renin (icRen) with regard to their endogenous expression and functions in vivo using isoform-specific knockout mice. The major findings of this thesis are: 1) sRen and icRen are independently transcribed using different promoters, 2) icRen is the major form of renin in adult mouse brain, 3) there is a developmental shift in utilization of renin isoforms in the mouse brain, 4) peripheral sRen (mostly from the kidney) is crucial for survival and maintenance of normal blood pressure, and 5) depletion of sRen from either neuronal or glial cells in the brain is insufficient to alter blood pressure.