Elucidation of molecular pathomechanism and development of therapy for collagen VI deficiency

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293214
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: NISHINO Ichizo 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 疾病研究第一部, 部長 (00332388)
• Co-Investigator(Kenkyū-buntansha): 野口 悟 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 疾病研究第一部, 室長 (00370982) ; 西川 敦子 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 疾病研究第一部, 研究員 (70737262)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 遺伝病 / 骨格筋 / 治療 / コラーゲン / 間質前駆細胞

Outline of Final Research Achievements

Congenital muscular dystrophies with collagen VI deficiency are inherited muscle disorders are caused by mutations in one of COL6A1-3 genes. Muscle pathology is characterized by fiber size variation and increased interstitial fibrosis and fat infiltration. In this study, we define critical events that contribute to muscle weakness and fibrosis in mouse models with collagen VI deficiency. The Col6a1 mutant mice develop non-progressive weakness from younger age, accompanied by stunted muscle growth due to reduced IGF-1 signaling activity. In addition, these mutant mice have high numbers of interstitial mesenchymal progenitor cells, which dramatically increase with repeated myofiber necrosis/regeneration. Our results suggest that impaired neonatal muscle growth and the activation of the mesenchymal cells in skeletal muscles contribute to the pathology of collagen VI-deficient muscle diseases, and more importantly, provide the insights on the therapeutic strategies for the disease.

Free Research Field

筋病学