2021 Fiscal Year Final Research Report
Investigation of the potential involvement of LBX1 in the development of adolescent idiopathic scoliosis
| Project/Area Number |
19K09660
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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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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Keio University (2020-2021)
National Defense Medical College (2019) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
堀内 圭輔 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 整形外科学, 准教授 (30327564)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | LBX1 / 脊柱変形 / マウスモデル / 思春期突発性側弯症 |
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| Outline of Final Research Achievements |
LBX1 is a gene located near a single nucleotide polymorphism that is highly associated with susceptibility to adolescent idiopathic scoliosis. However, the potential involvement of LBX1 in the etiology of this spinal deformity has not been elucidated. In this study, we aimed to determine whether the lack of LBX1 in skeletal muscle results in spinal deformities in mice. We generated mutant mice in which the Lbx1 allele was conditionally excised under the control of a human muscle actin promoter. Mice lacking LBX1 from the skeletal muscle were fertile and available. The mutant mice had hypoplastic forelimbs and weighed less than control animals, but otherwise, there were no overt anomalies. The mice did not exhibit a scoliosis-like spinal deformity; however, they developed moderate kyphosis as they grew old. These observations indicated that LBX1 is involved in limb development and potentially in the maintenance of spinal alignment in mice.
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| Free Research Field |
整形外科学
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| Academic Significance and Societal Importance of the Research Achievements |
思春期突発性側弯症は多因子疾患であり，その発症には遺伝的素因や後天的な要素が関与していると考えられる．また，これまでの研究から，思春期突発性側弯症患者は健常な対象群と比較して痩せ体形であることが明らかとなっている．LBX1が体組成もしくはエネルギー代謝に関与しているという報告は従来なく，今回のマウスモデルから得られた知見は，このヒト側弯症患者との類似性があり，側弯症患者の病態を考える上で重要であると考える．さらに，本研究の成果から，LBX1の機能不全は，体組成の変化を誘導し，その結果間接的に脊柱側弯症の発生リスクを増加させる可能性が示唆された．
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