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: 7064990
• 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/7064990
• 关键词: blood chemistry; bone; bone development; bone metabolism; calcium ion; cell growth regulation; developmental genetics; fluorescent dye /probe; gene expression; gene mutation; genetic regulation; growth /development; histology; homeostasis; in situ hybridization; ion transport; kidney disorder; kidney function; magnesium ion; membrane channels; nonmammalian vertebrate embryology; polymerase chain reaction; predoctoral investigator; protein structure function; zebrafish

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（由申请人提供）：斑马鱼trpm7突变体表现出肾结石形成、生长迟缓和骨骼发生缺陷。本研究的目的是确定 trpm7 在调节生理 Mg2+ 和 Ca2+ 稳态和肾功能中的作用，提供改变骨发育调节的机制，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，将通过血清学测定评估生理 Mg2+ 和 Ca2+ 水平，通过荧光标记染料评估体内肾功能，并通过原位杂交和定量 RT-PCR 确定阳离子稳态和骨发育调节因子的基因表达模式和水平的变化。建立 trpm7 介导的这些发育过程调节机制将有助于深入了解在人类中观察到的因阳离子稳态改变、肾功能衰竭和甲状旁腺功能亢进而导致的类似发育缺陷。此外，了解 trpm7 介导的调节机制可能会导致治疗这些疾病的新靶标。