Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor(s)

Dr. Dale Laird

Abstract

Connexins (Cxs) and pannexins (Panxs) are protein families that form large-pore channels which exist at the plasma membrane for both intracellular and extracellular signaling. Given their potential for overlapping cellular signaling functions we proposed that mice lacking both a connexin and a pannexin would have a severe phenotype. To investigate this possibility we crossed Panx1 null mice with Cx40 knockout mice and characterized the first global connexin/pannexin double knockout mouse. Intriguingly, the combined ablation of both Cx40 and Panx1 caused decreased prenatal and newborn survival, but did not affect the fertility or lifespan of surviving mice. Cx40-/- and Cx40-/-Panx1-/- mice had cardiac hypertrophy, and furthermore, combined channel ablation led to increasing severe hypertension and decreased endothelium dependent vasodilation in Cx40-/-Panx1-/- mice. Overall, these studies suggest that even though Panx1 and Cx40 act via differential mechanisms, they have a co-regulatory role in certain physiological processes such as vascular response.

Available for download on Sunday, October 11, 2020


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