Age-related and mutation-independent proteomic changes in dystrophic mouse muscle

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07544
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Aoki Yoshitsugu 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 遺伝子疾患治療研究部, 部長 (80534172)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: デュシェンヌ型筋ジストロフィー / サルコペニア / 筋萎縮 / 速筋型タイプII筋線維 / 超高感度定量質量分析 / 加齢 / 骨格筋

Outline of Final Research Achievements

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease characterised by loss of ambulation and cardiorespiratory problems. At this moment, many aspects of the pathology and disease progression over time are still unclear. Here, we have utilised high-resolution isoelectric focusing liquid chromatography-mass spectrometry to investigate differential protein expression in the tibialis anterior (TA) of mdx, mdx52 and wild-type controls (C57BL/6) at 8, 16 and 80 weeks of age. This technique has provided improved resolution of the proteome, whereby 4974 proteins were detected in all samples. Only slight differences in protein expression were observed between mdx and mdx52. This analysis showed apparent differences between the control and two dystrophic mice with 2148 proteins differentially expressed (t-Test, P=0.01). Additionally, protein expression changed significantly with ageing for both groups.

Free Research Field

神経内科学関連

Academic Significance and Societal Importance of the Research Achievements

本研究成果は筋萎縮の複雑な分子病態の解明に基づき、筋ジストロフィーおよび社会的課題であるサルコペニアの克服につながる。