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https://hdl.handle.net/20.500.14094/90006942
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2024-04-25
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90006942 (fulltext)
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メタデータID
90006942
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open access
出版タイプ
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タイトル
Trimerization and genotype-phenotype correlation of COL4A5 mutants in Alport syndrome
著者
Kamura, Misato ; Yamamura, Tomohiko ; Omachi, Kohei ; Suico, Mary Ann ; Nozu, Kandai ; Kaseda, Shota ; Kuwazuru, Jun ; Shuto, Tsuyoshi ; Iijima, Kazumoto ; Kai, Hirofumi
著者名
Kamura, Misato
著者ID
A0868
研究者ID
1000030770242
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=cead95bcb1b9c2ee520e17560c007669
著者名
Yamamura, Tomohiko
山村, 智彦
ヤマムラ, トモヒコ
所属機関名
医学研究科
著者名
Omachi, Kohei
著者名
Suico, Mary Ann
著者ID
A1366
研究者ID
1000070362796
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=cfe7f9e40ab7db60520e17560c007669
著者名
Nozu, Kandai
野津, 寛大
ノヅ, カンダイ
所属機関名
医学研究科
著者名
Kaseda, Shota
著者名
Kuwazuru, Jun
著者名
Shuto, Tsuyoshi
著者ID
A0877
研究者ID
1000000240854
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=1a50a9148347284a520e17560c007669
著者名
Iijima, Kazumoto
飯島, 一誠
イイジマ, カヅモト
所属機関名
医学研究科
著者名
Kai, Hirofumi
収録物名
Kidney International Reports
出版者
Elsevier
刊行日
2020-01-30
公開日
2020-03-24
抄録
Introduction: Alport syndrome is a hereditary glomerulonephritis that results from the disruption of collagen α345(IV) heterotrimerization caused by mutation in COL4A3, COL4A4 or COL4A5 genes. Many clinical studies have elucidated the correlation between genotype and phenotype, but there is still much ambiguity and insufficiency. Here, we focused on the α345(IV) heterotrimerization of α5(IV) missense mutant as a novel factor to further understand the pathophysiology of Alport syndrome. Methods: We selected 9 α5(IV) missense mutants with typical glycine substitutions that clinically differed in disease progression. To quantify the trimerization of each mutant, split nanoluciferase-fused α3/α5 mutants and α4 were transfected into the cells, and intracellular and secreted heterotrimer were detected by luminescence using an assay that we developed previously. Results: Trimer formation and secretion patterns tended to be similar to the wild type in most of the mutations that did not show proteinuria at a young age. On the other hand, trimer secretion was significantly reduced in all the mutations that showed proteinuria and early onset of renal failure. One of these mutants has low ability of intracellular trimer formation, and the others had the defect of low-level secretion. In addition, the mutant that is assumed to be nonpathogenic has similar trimer formation and secretion pattern as wild-type α5(IV). Conclusion: The result of cell-based α345(IV) heterotrimer formation assay was largely correlated with clinical genotype–phenotype. These trimerization assessments provide additional phenotypic considerations and may help to distinguish between pathogenic and nonpathogenic mutations.
キーワード
Alport syndrome
COL4A5 mutation
collagen trimerization
genotype–phenotype
split nanoluciferase
カテゴリ
医学研究科
学術雑誌論文
権利
© 2020 International Society of Nephrology. Published by Elsevier Inc.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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資源タイプ
journal article
言語
English (英語)
eISSN
2468-0249
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関連情報
DOI
https://doi.org/10.1016/j.ekir.2020.01.008
URI
https://www.kobe-u.ac.jp/research_at_kobe/NEWS/news/2020_03_10_01.html
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