TRANSGENIC ANALYSIS OF CA SENSING RECEPTOR IN THE KIDNEY
TRANSGENIC ANALYSIS OF CA SENSING RECEPTOR IN THE KIDNEY
批准号:
2905178
负责人:
JOSHUA M KAPLAN
金额:
$4.0万
依托单位国家:
美国
项目类别:
财政年份:
1999
资助国家:
美国
项目状态:
未结题
起止时间:
1999-07-01 至
中文摘要
细胞外钙敏感受体(CaSR)很可能在
钙及其受体在调节肾脏对钙的反应中的重要作用
其他电解液的加工,但其确切的功能和
其在肾脏中的作用机制尚未阐明。至
确定CaSR在转基因小鼠肾脏中的作用
CaSR在肾脏远端小管中的过度表达将是
发展起来,过度表达和随后增加的影响
钙激活受体对全动物生理和细胞生理学的激活作用
检查过了。钙激活受体在远曲小管中的作用
肾对肾钙的重吸收,一次浓缩
能力、心尖钾通道活性和环磷酸腺苷的产生
对加压素的反应将被确定。
这项工作的潜在临床意义是深远的。
确定CaSR在肾脏中的作用必将有助于阐明
由CaSR突变引起的罕见的遗传疾病,但它
还应提高对以下主要流程的理解
肾结石,骨质疏松症,甲状旁腺疾病,可能
甚至是原发性高血压。
英文摘要
The extracellular calcium-sensing receptor (CaSR) most likely plays a
critical role in modulating the kidney's response to calcium and its
processing of other electrolytes, but its exact function and
mechanisms of action in the kidney have yet to be elucidated. To
determine the role of CaSR in the kidney, a transgenic mouse model
over expressing the CaSR in the distal tubules of the kidney will be
developed and the effect of over expression and subsequent increased
activation of CaSR on whole animal physiology and cellular physiology
examined. The effect of activation of CaSR in the distal tubules of
the kidney on renal calcium reabsorption, uniary concentrating
ability, apical potassium channel activity, and cyclic-AMP generation
in response to vasopressin will be determined.
The potential clinical significance of this work is far-reaching.
Determine the role of CaSR in the kidney will certainly shed light on
the rare genetic disorders resulting from mutations in CaSR, but it
should also improve understanding of primary processes in
nephrolithiasis, osteoporosis, parathyroid disorders, and possibly
even essential hypertension.
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