2000 Fiscal Year Final Research Report Summary
Study on signal transduction system through calcium-sensing receptor
| Project/Area Number |
11671082
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
FUKUMOTO Seiji University of Tokyo Branch Hospital Department of Medicine Lecturer, 医学部・附属病院・分院, 講師 (30202287)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Yasuhiro University of Tokyo Branch Hospital Department of Medicine Assistant Professor, 医学部・附属病院・分院, 助手 (50202164)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Calcium-sensing receptor / Promoter / Cloning / Hypercalcemia / Hypocalcemia / Mutation |
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| Research Abstract |
1.Study on mutations of calcium-sensing receptor(CaSR)
Inactivating mutations of CaSR cause familial hypocalciuric hypercalcemia(FHH)and neonatal severe hyperparathyroidism(NSHPT), while activating mutations of CaSR result in autosomal dominant hypocalcemia(ADH). NSHPT is usually caused by homozygous inactivating mutations of CaSR and has been proposed to be fatal if parathyroid glands were removed during infancy. We have identified novel mutations of CaSR and shown that the patient with homozygous inactivating mutation of CaSR can survive into adulthood without any treatment, if the functional impairment of the mutant CaSR is mild. We have also shown that histological appearance of parathyroid glands in patients with inactivating mutations of CaSR is different from that in patients with primary hyperparathyroidism.
2.Cloning of promoter region of human CaSR gene
In addition to mutations of CaSR, derangements of expression of this receptor may result in abnormal Ca metabolism. In order to understand the regulatory mechanisms for expression of CaSR, we have cloned promoter region of human CaSR gene. Human CaSR gene has at lease two promoters and produces multiple mRNAs by alternate aplicing. Expression levels of CaSR mRNA driven by the upstream promoter were specifically reduced in parathyroid adenomas. Elucidation of regulatory factors of these promtoers is necessary for understanding pathogenesis of derangements of Ca metabolism.
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[Publications] Okazaki R, Chikatsu N, Nakatsu M, Takeuchi Y, Ajima M, Miki J, Fujita T, Arai M, Totsuka Y, Tanaka K, Fukumoto S: "A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia"J Clin Endocrinol Metab. 84. 363-366 (1999)
Description
「研究成果報告書概要(欧文)」より
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