Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biology

Supervisor

Drysdale, Tom A.

2nd Supervisor

Kelly, Gregory M.

Co-Supervisor

Abstract

Chronic kidney disease (CKD) is a substantial global health burden that has recently been linked to the genetic locus SHROOM3 by several genome-wide association studies. Shroom3 is an actin-binding protein that is necessary for inducing apical constriction in epithelial cells. Our lab has previously shown that Shroom3 is critical for proper kidney development and loss of Shroom3 produces symptoms associated with CKD. As hypertension is both a leading cause and comorbidity of CKD, I hypothesized that loss of Shroom3 confers increased susceptibility to hypertension. Using a high-salt induced model of hypertension, I show that Shroom3 deficient mice do not become hypertensive but exhibit an increased salt-sensitive blood pressure response. Additionally, I show that human SHROOM3 variants currently identified within our population have attenuated apical constriction activity. Collectively, the findings from our in vivo and in vitro work implicate the consequences of reduced Shroom3 function in the pathophysiology of human disease.

Available for download on Monday, March 23, 2020

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