Functional analyses of SMPDL3A as a candidate gene of congenital radioulnar synostosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09572
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Shinshu University
• Principal Investigator: Nakamura Yukio 信州大学, 医学部, 特任教授 (00549488)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 遺伝子 / 骨格発生 / 形態形成

Outline of Final Research Achievements

In this study, SMPDL3A was identified using whole exome suquencing as candidate genes of congenital radioulnar synostosis (CRUS). Amino acid similarities of SMPDL3A were approximately 54% across humans and zebrafish, which is quite high. In situ hybridization analyses revealed that the strong expression was detected in the craniofacial and pectoral fin regions of zebrafish embryos and larvae. Also, the genetically-modified zebrafish showed that SMPDL3A regulates BMP signaling during skeletogenesis. Furthermore, SMPDL3A containing potentially the disease-causing mutations, had reduced activity of BMP or Wnt signaling.

Free Research Field

遺伝学

Academic Significance and Societal Importance of the Research Achievements

全エクソン解析により先天性橈尺骨癒合症の候補遺伝子としてSMPDL3Aを同定した。。
本研究では骨格形態・形成過程におけるSMPDL3A遺伝子の分子メカニズムを明らかにすることにより、先天性橈尺骨癒合症の病態に迫る。骨格形態・形成過程におけるSMPDL3A遺伝子の分子メカニズムを世界に先駆けて実証しており、ヒトの正常な骨格発生・分化の理解のみならず、骨系統疾患の病態に繋がると期待できる。