文献

J-GLOBAL ID：202002289938863274   整理番号：20A2576994

胆管-アトレシア関連マンノシダーゼ-1-Alpha-2遺伝子は胆管および繊毛形態形成および側性を調節する【JST・京大機械翻訳】

Biliary-Atresia-Associated Mannosidase-1-Alpha-2 Gene Regulates Biliary and Ciliary Morphogenesis and Laterality

著者 (34件)： So Juhoon (Department of Developmental Biology, McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States) ,  Ningappa Mylarappa (Hillman Center for Pediatric Transplantation of the Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States) ,  Glessner Joseph (Center for Applied Genomics of the Children’s Hospital of Philadelphia, Philadelphia, PA, United States) ,  Min Jun (Departments of Bioengineering, Cellular and Molecular Medicine, and Computer Science and Engineering, University of California San Diego, La Jolla, CA, United States) ,  Ashokkumar Chethan (Hillman Center for Pediatric Transplantation of the Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States) ,  Ranganathan Sarangarajan (Division of Pediatric Pathology, Department of Pathology, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States) ,  Higgs Brandon W. (Hillman Center for Pediatric Transplantation of the Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States) ,  Li Dong (Center for Applied Genomics of the Children’s Hospital of Philadelphia, Philadelphia, PA, United States) ,  Sun Qing (Hillman Center for Pediatric Transplantation of the Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States) ,  Schmitt Lori (Histology Core Laboratory, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States) ,  Biery Amy C. (Division of Pediatric Pathology, Department of Pathology, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States) ,  Dobrowolski Steven (Division of Pediatric Pathology, Department of Pathology, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States) ,  Trautz Christine (Hillman Center for Pediatric Transplantation of the Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States) ,  Fuhrman Leah (Hillman Center for Pediatric Transplantation of the Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States) ,  Schwartz Molly Christine (Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA, United States) ,  Klena Nikolai Thomas (Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA, United States) ,  Fusco Joseph (Pediatric General and Thoracic Surgery, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States) ,  Prasadan Krishna (Pediatric General and Thoracic Surgery, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States) ,  Adenuga Morayooluwa (Hillman Center for Pediatric Transplantation of the Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States) ,  Mohamed Nada (Pediatric General and Thoracic Surgery, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States) ,  Yan Qi (Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States) ,  Chen Wei (Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States) ,  Horne William (Richard King Mellon Foundation Institute for Pediatric Research, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States) ,  Dhawan Anil (Paediatric Liver, GI, and Nutrition, King’s College Hospital, London, United Kingdom) ,  Sharif Khalid (Children’s Hospital of Birmingham, Birmingham, United Kingdom) ,  Kelly Deirdre (Children’s Hospital of Birmingham, Birmingham, United Kingdom) ,  Squires Robert H (Pediatric Gastroenterology, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States) ,  Gittes George K. (Pediatric General and Thoracic Surgery, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States) ,  Hakonarson Hakon (Center for Applied Genomics of the Children’s Hospital of Philadelphia, Philadelphia, PA, United States) ,  Morell Victor (Division of Cardiac Surgery, Department of Cardiothoracic Surgery, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States) ,  Lo Cecilia (Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA, United States) ,  Subramaniam Shankar (Departments of Bioengineering, Cellular and Molecular Medicine, and Computer Science and Engineering, University of California San Diego, La Jolla, CA, United States) ,  Shin Donghun (Department of Developmental Biology, McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States) ,  Sindhi Rakesh (Hillman Center for Pediatric Transplantation of the Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States)
資料名： Frontiers in Physiology (Web)  (Frontiers in Physiology (Web))
巻： 11  ページ： 538701  発行年： 2020年 
JST資料番号： U7093A  ISSN： 1664-042X  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： スイス (CHE)  言語： 英語 (EN)

抄録/ポイント： 背景/目的:感染および遺伝的因子は,それぞれ,孤立性胆道閉鎖症(BA)または症候性BAで,主要な肝外異常を伴う。しかし,分離したBAは,マイナーな肝外腸および心血管異常および複数の感受性遺伝子とも関連しており,共通の起源を示唆する。方法:BAサブタイプとは無関係に,肝臓移植を必要とするBAにおけるゲノムワイド関連,標的化配列決定および組織染色による新規感受性遺伝子を検討した。形態形成,発生経路,および繊毛形成に及ぼすCandidate遺伝子効果を,ゼブラフィッシュノックダウンとマウスノックアウトモデル,マウス気道細胞培養,および肝臓トランスクリプトーム分析で調査した。【結果】マンノシダーゼ-1-α-2(MAN1A2)における一塩基多型は,BAと有意に関連し,MAN1A2発現に影響を及ぼすことが知られている他の多型とは関連していたが,BAサブタイプにおいて異なっては濃縮されなかった。ゼブラフィッシュ胚において,man1a2ノックダウンは,不良な胆汁ネットワーク形成,Kupffer小胞,心臓と肝臓ヘテロタクシーにおける毛様体形成不全,および調節不全のegfraと他の発生遺伝子を引き起こした。準最適ヒト1a2ノックダウンは,EGFR経路遺伝子,アデノシンリボシル化因子-6の準最適EGFRシグナリングまたは最適以下のノックダウンと協力し,これは,それぞれ,最小効果を有し,胆管欠損を再現し,ヘテロタクシーではなかった。培養マウス気道上皮において,Man1a2ノックダウンは繊毛発生と運動性を停止した。呼吸不全を経験したMan1a2-/-マウスは,門脈および胆管炎症も示した。ヒトBA肝臓とMan1a2-/-肝臓は,多系ヒト側性欠損を引き起こすことが知られている,Man1a2発現の減少と調節不全毛様体遺伝子を示した。【結論】MAN1A2.man1a2における配列変異体と関連するBAは,ゼブラフィッシュおよびマウスにおける繊毛形成を調節することにより,肝胆道形態形成に加えて,側性を調節し,BAにおける多系統欠損の新しい発達基盤を提供する。Copyright 2020 The Author(s) All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： 心臓 ,  *遺伝 ,  *遺伝子 ,  気道 ,  細胞培養 ,  胆汁 ,  ヒト ,  *繊毛 ,  *形態形成 ,  *胆管 ,  *マンノシダーゼ ,  タクシー ,  ゼブラフィッシュ ,  ターゲティング ,  EGF受容体

著者キーワード (5件)： 胆道閉鎖症 ,  肝移植 ,  繊毛 ,  胆管形態形成 ,  側性

分類 (1件)： 発生と分化  (EJ16020W)

引用文献 (33件)：

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タイトルに関連する用語 (7件)： 胆管 ,  マンノシダーゼ ,  遺伝子 ,  繊毛 ,  形態形成 ,  側性 ,  調節