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Functional analysis of SNP mutations leading to single amino acid substitution in NBCe1
https://doi.org/10.15083/00004078
https://doi.org/10.15083/00004078ba7b7d6d-e816-4745-b1df-688d05da78d6
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
h22_yamazaki.pdf (2.1 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-11-08 | |||||
| タイトル | ||||||
| タイトル | Functional analysis of SNP mutations leading to single amino acid substitution in NBCe1 | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | pRTA | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | SLC4A4 | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | SNP | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | renal proximal tubules | |||||
| 資源タイプ | ||||||
| 資源 | http://purl.org/coar/resource_type/c_46ec | |||||
| タイプ | thesis | |||||
| ID登録 | ||||||
| ID登録 | 10.15083/00004078 | |||||
| ID登録タイプ | JaLC | |||||
| その他のタイトル | ||||||
| その他のタイトル | Na+-HCO3-共輸送体(NBCe1)の単一アミノ酸置換を伴うSNP変異体の機能解析 | |||||
| 著者 |
Yamazaki, Osamu
× Yamazaki, Osamu |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 9418 | |||||
| 姓名 | 山崎, 修 | |||||
| 著者所属 | ||||||
| 著者所属 | 東京大学大学院医学系研究科内科学専攻 | |||||
| Abstract | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The electrogenic Na+-HCO3- cotransporter NBCe1 encoded by SLC4A4 plays essential roles in the regulation of intracellular/extracellular pH. Homozygous mutations in NBCe1 cause proximal renal tubular acidosis associated with ocular abnormalities. In the present study I tried to perform functional characterization of the 4 nonsynonymous single nucleotide polymorphisms (SNPs), E122G, S356Y, K558R, and N640I in NBCe1A. Functional analysis in Xenopus oocytes revealed that while the K558R variant had a significantly reduced transport activity corresponding to 47% of the wild-type activity, the remaining variants E122G, S356Y and N640I did not change the NBCe1A activity. Apparent Na+ affinity of K558R was not different from that of wild-type NBCe1A. Immunohistological analyses in HEK293 cells and MDCK cells indicated that none of these SNPs changed the trafficking behaviors of NBCe1A. Functional analysis in HEK293 cells also revealed that only the K558R variant had a reduced transport activity, corresponding to 41 - 47% of the wild-type activity. From these results I conclude that among 4 SNPs only the K558R variant, which is predicted to lie in transmembrane segment 5, significantly reduces the NBCe1A activity without changing the trafficking behavior or the apparent extracellular Na+ affinity. | |||||
| 書誌情報 | 発行日 2011-03-24 | |||||
| 日本十進分類法 | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 490 | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位 | ||||||
| 値 | doctoral | |||||
| 学位分野 | ||||||
| Medical Science(医学) | ||||||
| 学位授与機関 | ||||||
| 学位授与機関名 | University of Tokyo (東京大学) | |||||
| 研究科・専攻 | ||||||
| Department of Internal Medicine, Graduate School of Medicine (医学系研究科内科学専攻) | ||||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2011-03-24 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第27070号 | |||||
| 学位記番号 | ||||||
| 博医第3680号 | ||||||
