Analysis of Tmem161a function in bone metabolism using the exchangeable gene trap mutagenesis
| Project/Area Number |
17K11017
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
帖佐 悦男 宮崎大学, 医学部, 教授 (00236837)
舩元 太郎 宮崎大学, 医学部, 講師 (20404452)
荒木 正健 熊本大学, 生命資源研究・支援センター, 准教授 (80271609)
荒木 喜美 熊本大学, 生命資源研究・支援センター, 教授 (90211705)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Tmem161a遺伝子 / 骨代謝機能 / 骨芽細胞 / 可変型遺伝子トラップ法 / ロコモティブシンドローム / モデルマウス |
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| Outline of Final Research Achievements |
We analyzed the bone phenotype of Transmembrane161a (Tmem161a) gene trap line produced by the exchageable gene trap method. Tmem161a expression in femur was observed in articular cartilage, proliferative zone of growth plate and osteoblasts by X-gal staining. Compared with wild type, bone structure of trap mice femur was dense in μCT and there were significant differences in bone morphometric analysis. In biomechanical strength analysis, trap mice indicated significant strength.In HE staining, cortical bone thickness was thick and primary trabecular bone was also large. We performed realtime PCR and confirmed increased expression BMP4 and Runx2. Increased expression of Runx2 and Osterix and increased calcification were observed in primary osteoblast culture. Similar results were obtained in cell lines knocked out Tmem161a by CRISPR/Cas9 system.It seems that Tmem161a is involved in osteoblast function. There is a possibility that Tmem161a is a novel gene involved in bone metabolism.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は骨粗鬆症等のロコモティブシンドロームの病因病態解明の為に、可変型遺伝子トラップ法により樹立した変異マウス系統を用いて、骨軟骨代謝に関与する新規遺伝子群探索の効率的なスクリーニングを実施している。我々はそれらトラップクローンデータをEGTCデータベース(http://egtc.jp) に公開し、骨軟骨代謝に異常をきたす疾患モデルマウスライブラリーを構築している。
そのライブラリーマウスの中で、Tmem161a遺伝子欠損マウスは、骨軟骨スクリーニングにおいて明らかな骨表現型異常を呈していた。これまでTmem161a遺伝子の骨代謝について報告例はない為、学術的社会的意義は非常に高いと考えられる。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Development of an efficient screening system to identify novel bone metabolism-related genes using the exchangeable gene trap mutagenesis mouse models2017
Author(s)
Syuji Kurogi, Tomohisa Sekimoto, Taro Funamoto, Tomomi Ohta, Shihoko Nakamura, Takuya Nagai, Mai Nakahara, Kumiko Yoshinobu, Kimi Araki, Masatake Araki, Etsuo Chosa
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 40692-40692
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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