Pathomechanism and therapeutic strategy of Fukuyama congenital muscular dystrophy and related disorders

• Toda Tatsushi

  Division of Neurology, Kobe University Graduate School of Medicine

Bibliographic Information

Other Title

• シンポジウム５‐３　難治性筋疾患の病態機序‐ＣＫ発見から５０年‐治療の時代へ　福山型筋ジストロフィーおよび類縁疾患の病態・治療戦略
• 福山型筋ジストロフィーおよび類縁疾患の病態・治療戦略
• フクヤマガタ キンジストロフィー オヨビ ルイエン シッカン ノ ビョウタイ チリョウ センリャク

Abstract

Hypoglycosylation and reduced laminin-binding activity of α-dystroglycan are common characteristics of dystroglycanopathy, which is a group of congenital and limb-girdle muscular dystrophies. We previously identified the genes for Fukuyama congenital muscular dystrophy (FCMD) and muscle-eye-brain disease (MEB). FCMD, caused by a mutation in the fukutin gene, is a severe form of dystroglycanopathy. Knock-in mice carrying the founder retrotransposal insertion exhibited hypoglycosylated α-dystroglycan; however, no signs of muscular dystrophy were observed. More sensitive methods detected minor levels of intact α-dystroglycan, and solid-phase assays determined laminin binding levels to be approximately 50% of normal. In contrast, intact α-dystroglycan is undetectable in the dystrophic Large mouse, and laminin-binding activity is markedly reduced. These data indicate that a small amount of intact α-dystroglycan is sufficient to maintain muscle cell integrity in knock-in mice, suggesting that the treatment of dystroglycanopathies might not require the full recovery of glycosylation. Transfer of fukutin into knock-in mice restored glycosylation of α-dystroglycan. Transfer of LARGE produced laminin-binding forms of α-dystroglycan in both knock-in mice and the POMGnT1 mutant mouse. These data suggest that even partial restoration of α-dystroglycan glycosylation and laminin-binding activity by replacing or augmenting glycosylation-related genes might effectively deter dystroglycanopathy progression and thus provide therapeutic benefits.<br>

Journal

• Rinsho Shinkeigaku

  Rinsho Shinkeigaku 49 (11), 859-862, 2009

  Societas Neurologica Japonica

Keywords

• Fukuyama congenital muscular dystrophy
• fukutin
• dystroglycanopathy
• LARGE
• sugar chain

Details

• CRID: 1390001205036478208
• NII Article ID: 10026290982
• NII Book ID: AN00253207
• DOI: 10.5692/clinicalneurol.49.859
• ISSN: 18820654
• ISSN: 0009918X
• NDL BIB ID: 10515778
• PubMed: 20030231
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10515778
• Web Site: https://search.jamas.or.jp/link/ui/2010076445
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed