Claudin-4 and calcium homeostasis
Co-Applicant(s): R. Todd Alexander
Lay Abstract
Background: Affecting roughly 1 in 10 Canadians, kidney stones are painful and on the rise. These stones are usually caused by an accumulation of calcium in the urine. Their occurrence depends on individuals’ diet, health status, lifestyle and family history. Our collaborator Dr. Fuster (University of Bern, Switzerland) has identified kidney stone formers with two variations in a renal protein called claudin-4. This protein contributes to ion balance in the body.
Purpose: We will conduct experiments to understand how mutated claudin-4 proteins alter the ability of the kidney to maintain proper ion composition in the urine and result in urinary calcium accumulation.
Methods: Using kidney cells that express the normal or mutant proteins and mice that lack claudin-4, we will examine how these variations affect the claudin-4 protein ‘s abundance, stability and localization. We will also examine claudin-4 effects on the amount of urinary calcium and on other calcium transporting proteins in these mice.
Anticipated outcomes: claudin-4 mutants are expected to reduce calcium reabsorption in kidney cells and the role of claudin-4 in calcium regulation will be clarified in mice.
Relevance to Patients/Community: These experiments will identify a novel gene involved in regulation of urinary calcium and a potential new target to treat these common conditions. Background: Affecting roughly 1 in 10 Canadians, kidney stones are painful and on the rise. These stones are usually caused by an accumulation of calcium in the urine. Their occurrence depends on individuals’ diet, health status, lifestyle and family history. Our collaborator Dr. Fuster (University of Bern, Switzerland) has identified kidney stone formers with two variations in a renal protein called claudin-4. This protein contributes to ion balance in the body.
Purpose: We will conduct experiments to understand how mutated claudin-4 proteins alter the ability of the kidney to maintain proper ion composition in the urine and result in urinary calcium accumulation.
Methods: Using kidney cells that express the normal or mutant proteins and mice that lack claudin-4, we will examine how these variations affect the claudin-4 protein ‘s abundance, stability and localization. We will also examine claudin-4 effects on the amount of urinary calcium and on other calcium transporting proteins in these mice.
Anticipated outcomes: claudin-4 mutants are expected to reduce calcium reabsorption in kidney cells and the role of claudin-4 in calcium regulation will be clarified in mice.
Relevance to Patients/Community: These experiments will identify a novel gene involved in regulation of urinary calcium and a potential new target to treat these common conditions.
