Zebrafish trpm7 roles in bone and kidney function

描述（由申请人提供）：斑马鱼trpm7突变体表现为肾结石形成、生长迟缓和骨骼形成缺陷。本研究的目的是建立trpm7在调节生理Mg2+和Ca2+稳态和肾功能中的作用，提供骨发育调节改变的机制，并阐明trpm7活性在调节生长、骨发育和正常肾功能中的时间要求。在trpm7突变体中，生理Mg2+和Ca2+水平将通过血清学检测来评估，肾脏功能将通过荧光标记染料在体内评估，阳离子稳态和骨发育调控基因表达模式和水平的变化将通过原位杂交和定量RT-PCR来确定。建立trpm7介导的这些发育过程的调节机制，将有助于深入了解在人类中观察到的由阳离子稳态改变、肾功能衰竭和甲状旁腺功能亢进引起的类似发育缺陷。此外，了解trpm7介导的调节机制可能会为治疗这些疾病带来新的靶点。

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.