『徳島大学 教育・研究者情報データベース (EDB)』---[学外] /
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EID=318262EID:318262, Map:0, LastModified:2016年11月17日(木) 11:08:15, Operator:[三木 ちひろ], Avail:TRUE, Censor:0, Owner:[遠藤 逸朗], Read:継承, Write:継承, Delete:継承.
種別 (必須): 学術論文 (審査論文) [継承]
言語 (必須): 英語 [継承]
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カテゴリ (推奨):
共著種別 (推奨):
学究種別 (推奨):
組織 (推奨):
著者 (必須): 1. (英) Dong Bingzi (日) (読)
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2.遠藤 逸朗 ([徳島大学.大学院医歯薬学研究部.保健科学域.保健科学部門.医用検査学系.生体機能解析学])
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3. (英) Ohnishi Yukiyo (日) (読)
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4.近藤 剛史
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5. (英) Hasegawa Tomoka (日) (読)
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6. (英) Amizuka Norio (日) (読)
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7. (英) Kiyonari Hiroshi (日) (読)
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8. (英) Shioi Go (日) (読)
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9.安倍 正博 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.血液・内分泌代謝内科学])
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10.福本 誠二 ([徳島大学.先端酵素学研究所.オープンイノベーション領域])
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11.松本 俊夫
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題名 (必須): (英) Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH).  (日)    [継承]
副題 (任意):
要約 (任意): (英) Activating mutations of calcium-sensing receptor (CaSR) cause autosomal dominant hypocalcemia (ADH). ADH patients develop hypocalcemia, hyperphosphatemia, and hypercalciuria, similar to the clinical features of hypoparathyroidism. The current treatment of ADH is similar to the other forms of hypoparathyroidism, using active vitamin D3 or parathyroid hormone (PTH). However, these treatments aggravate hypercalciuria and renal calcification. Thus, new therapeutic strategies for ADH are needed. Calcilytics are allosteric antagonists of CaSR, and may be effective for the treatment of ADH caused by activating mutations of CaSR. In order to examine the effect of calcilytic JTT-305/MK-5442 on CaSR harboring activating mutations in the extracellular and transmembrane domains in vitro, we first transfected a mutated CaSR gene into HEK cells. JTT-305/MK-5442 suppressed the hypersensitivity to extracellular Ca(2+) of HEK cells transfected with the CaSR gene with activating mutations in the extracellular and transmembrane domains. We then selected two activating mutations locating in the extracellular (C129S) and transmembrane (A843E) domains, and generated two strains of CaSR knock-in mice to build an ADH mouse model. Both mutant mice mimicked almost all the clinical features of human ADH. JTT-305/MK-5442 treatment in vivo increased urinary cAMP excretion, improved serum and urinary calcium and phosphate levels by stimulating endogenous PTH secretion, and prevented renal calcification. In contrast, PTH(1-34) treatment normalized serum calcium and phosphate but could not reduce hypercalciuria or renal calcification. CaSR knock-in mice exhibited low bone turnover due to the deficiency of PTH, and JTT-305/MK-5442 as well as PTH(1-34) increased bone turnover and bone mineral density (BMD) in these mice. These results demonstrate that calcilytics can reverse almost all the phenotypes of ADH including hypercalciuria and renal calcification, and suggest that calcilytics can become a novel therapeutic agent for ADH.  (日)    [継承]
キーワード (推奨):
発行所 (推奨):
誌名 (必須): Journal of Bone and Mineral Research ([米国骨代謝学会])
(pISSN: 0884-0431, eISSN: 1523-4681)

ISSN (任意): 1523-4681
ISSN: 0884-0431 (pISSN: 0884-0431, eISSN: 1523-4681)
Title: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Title(ISO): J. Bone Miner. Res.
Supplier: American Society for Bone and Mineral Research
Publisher: Wiley
 (NLM Catalog  (Wiley  (Scopus  (CrossRef (Scopus information is found. [need login])
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(必須): 30 [継承]
(必須): 11 [継承]
(必須): 1980 1993 [継承]
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年月日 (必須): 西暦 2015年 7月 16日 (平成 27年 7月 16日) [継承]
URL (任意):
DOI (任意): 10.1002/jbmr.2551    (→Scopusで検索) [継承]
PMID (任意): 25967373    (→Scopusで検索) [継承]
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WOS (任意): 000363286900005 [継承]
Scopus (任意): 2-s2.0-84945482381 [継承]
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備考 (任意): 1.(英) Article.ELocationID: 10.1002/jbmr.2551  (日)    [継承]
2.(英) Article.PublicationTypeList.PublicationType: Journal Article  (日)    [継承]
3.(英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't  (日)    [継承]
4.(英) KeywordList.Keyword: BONE MODELING AND REMODELING  (日)    [継承]
5.(英) KeywordList.Keyword: DISORDERS OF CALCIUM/PHOSPHATE METABOLISM  (日)    [継承]
6.(英) KeywordList.Keyword: FGF23  (日)    [継承]
7.(英) KeywordList.Keyword: GENETIC ANIMAL MODELS  (日)    [継承]
8.(英) KeywordList.Keyword: HORMONE REPLACEMENT/RECEPTOR MODULATORS  (日)    [継承]
9.(英) KeywordList.Keyword: PTH  (日)    [継承]
10.(英) KeywordList.Keyword: VITAMIN D  (日)    [継承]

標準的な表示

和文冊子 ● Bingzi Dong, Itsuro Endo, Yukiyo Ohnishi, Takeshi Kondo, Tomoka Hasegawa, Norio Amizuka, Hiroshi Kiyonari, Go Shioi, Masahiro Abe, Seiji Fukumoto and Toshio Matsumoto : Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH)., Journal of Bone and Mineral Research, Vol.30, No.11, 1980-1993, 2015.
欧文冊子 ● Bingzi Dong, Itsuro Endo, Yukiyo Ohnishi, Takeshi Kondo, Tomoka Hasegawa, Norio Amizuka, Hiroshi Kiyonari, Go Shioi, Masahiro Abe, Seiji Fukumoto and Toshio Matsumoto : Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH)., Journal of Bone and Mineral Research, Vol.30, No.11, 1980-1993, 2015.

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