Analysis on the pathogenesis of idiopathic scoliosis using Gpr126 conditional knock-out mice

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16709
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Guo Long 国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (50784055)
• Research Collaborator: SHUKUNAMI chisa ; WANG zheng ; IKEGAWA shiro
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 側彎 / 思春期特発性側弯症 / GWAS / GPR126 / 多因子遺伝病 / ゲノム解析 / 分子病態 / ノックアウトマウス

Outline of Final Research Achievements

Adolescent Idiopathic Scoliosis（AIS）is a very common disease with a prevalence of 2-4% all over the world. Its treatment is a global medical and medico-social problem; however, its etiology and pathogenesis remain mostly unclarified.
In this study, we investigated GPR126（G-protein-coupled receptor 126）, one of the GWAS-identified gene in vitro and in vivo. We have clarified the function of genes involved in formation and development of the spine at the cell level using iPS cells, etc. We have also clarified special and temporal expression profiles of Gpr126 during the development of the spine in mouse. By using a tamoxifen-induced system, we have established a Gpr126 conditional knock-out mouse（Sox9-CreERT2;Gpr126fl/fl）, which would be a good tool of AIS genetic studies.

Free Research Field

疾患遺伝学、医学遺伝学、ゲノム医科学

Academic Significance and Societal Importance of the Research Achievements

AISは原因不明の難病で、全世界で、人口の2-4%に発症するcommon diseaseであり、その病因の解明、効果的な治療法の開発は、世界の医療、医療経済上の大きな課題となっている。しかし、その病因、病態は、ほとんど不明である。先にGWASによりいくつかの原因遺伝子が同定されたが、AISの分子病態の解明には繋がっていない。本研究は、GWASにより発見された遺伝子のひとつであるGPR126を突破口に、脊椎の形成、成長における遺伝子機能の解析を通じて、AISの分子病態を解明した。