Examination of AGBL5 gene in congenital scoliosis

• Project/Area Number: 15K10395
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Shinshu University
• Principal Investigator: Nakamura Yukio 信州大学, 学術研究院医学系(医学部附属病院), 講師 (00549488)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 遺伝子 / 骨系統疾患 / 生体内発現

Outline of Final Research Achievements

The etiology of congenital scoliosis, in which the occurrence is approximately 1 in 2000 birth, is largely unknown. This time, we newly identified the de novo mutation in the AGBL5 gene. Since this gene is highly conserved among the species, it is considered that its function is essential. In this study, we mainly used zebrafish model. Consequently, whole-mount ISH revealed that the expression was localized around head, eyes, and pectoral fins. Also, the morpholino-mediated knockdown showed the dorso-ventral patterning defects and the reguration of BMP signaling by AGBL5. In addition, mouse 10T1/2 cells showed that ALP activities were down-regulated by AGBL5 gene transfection.

Academic Significance and Societal Importance of the Research Achievements

ある病気の原因を同定し、その役割を明らかにすることができれば、病態の理解に繋がり、かつ将来的な新規の診断方法の確立や治療法の開発につながる。本研究成果により、これまで原因が不明であった先天性側弯症の新しい診断方法の確立や治療法の確立に繋がると期待でき、社会的な幅員ははかりしれない。