Zebrafish trpm7 roles in bone and kidney function

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DESCRIPTION (provided by applicant): Zebrafish trpm7 mutants exhibit kidney stone formation, growth retardation, and defects in skeletogenesis. The purpose of this study is to establish a role for trpm7 in regulating physiologic Mg2+ and Ca2+ homeostasis and renal function, provide a mechanism for the altered regulation of bone development, and elucidate the temporal requirements for trpm7 activity in regulating growth, bone development, and proper renal function. In trpm7 mutants, physiologic Mg2+ and Ca2+ levels will be assessed through serological assays, renal function will be evaluated in vivo through fluorescently labeled dyes, and changes in the patterns and levels of gene expression for regulators of cation homeostasis and bone development will be determined by in situ hybridization and quantitative RT-PCR. Establishing the mechanisms for trpm7-mediated regulation of these developmental processes will provide insight into similar developmental defects observed in humans resulting from altered cation homeostasis, renal failure, and hyperparathyroidism. Furthermore, understanding the mechanism(s) for trpm7-mediated regulation may lead to new targets for treatment of these conditions.