Zebrafish trpm7 roles in bone and kidney function

斑马鱼 trpm7 在骨和肾功能中的作用

• 批准号: 7231371
• 负责人: MICHAEL R ELIZONDO
• 金额: $ 3.07万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7231371
• 关键词: Alleles; Biological Assay; Bone Development; Cations; Condition; Defect; Deposition; Development; Developmental Process; Dyes; Exhibits; Fellowship; Gene Expression; Goals; Growth; Homeostasis; Human; Hyperparathyroidism; Hypocalcemia result; Hypomagnesemia; In Situ Hybridization; Kidney; Kidney Calculi; Kidney Failure; Label; Lead; Link; Maintenance; Mediating; Molecular; Mutation; Organ; Osteogenesis; Pattern; Physiological; Process; Purpose; Rate; Regulation; Renal function; Renal tubule structure; Reverse Transcriptase Polymerase Chain Reaction; Role; Serological; Siblings; Staging; Testing; Tetracycline; Tetracyclines; Zebrafish; base; bone; early embryonic stage; in vivo; insight; mineralization; mutant; receptor

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.

描述(申请人提供)：斑马鱼trpm7突变体表现为肾结石形成、生长迟缓和骨骼生成缺陷。本研究的目的是确定trpm7在调节生理性镁、钙稳态和肾功能中的作用，为改变骨发育的调节机制提供机制，并阐明trpm7活性在调节生长、骨发育和正常肾功能方面的时间需求。在trpm7突变体中，生理性的镁和钙水平将通过血清学分析来评估，肾功能将通过荧光标记的染料在体内进行评估，阳离子平衡和骨发育调节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阳离子平衡改变、肾功能衰竭和甲状旁腺功能亢进在人类中观察到的类似发育缺陷。此外，了解trpm7介导的调控机制(S)可能会为治疗这些疾病带来新的靶点。