Zebrafish trpm7 roles in bone and kidney function

描述（由申请人提供）：斑马鱼trpm 7突变体表现出肾结石形成、生长迟缓和骨骼发生缺陷。本研究的目的是建立一个作用，为trpm 7在调节生理Mg 2+和Ca 2+稳态和肾功能，提供了一种机制，改变调节骨发育，并阐明了时间要求的trpm 7活性调节生长，骨发育和适当的肾功能。在trpm 7突变体中，将通过血清学试验评估生理Mg 2+和Ca 2+水平，将通过荧光标记染料在体内评价肾功能，并将通过原位杂交和定量RT-PCR确定阳离子稳态和骨发育调节剂的基因表达模式和水平的变化。建立trpm 7介导的这些发育过程的调节机制，将提供洞察类似的发展缺陷，在人类中观察到的阳离子稳态改变，肾功能衰竭，甲状旁腺功能亢进。此外，了解trpm 7介导的调节机制可能会导致治疗这些疾病的新靶点。

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.