Biochemical and ultrastructural evidence of endoplasmic reticulum stress in LGMD2I

Chiara A. Boito, Marina Fanin, Bruno F. Gavassini, Giovanna Cenacchi, Corrado Angelini, Elena Pegoraro

Research output: Contribution to journalArticle

Abstract

Limb girdle muscular dystrophy type 2I (LGMD2I) is due to mutations in the fukutin-related protein gene (FKRP), encoding a putative glycosyltransferase involved in α-dystroglycan processing. To further characterize the molecular pathogenesis of LGMD2I, we conducted a histological, immunohistochemical, ultrastructural and molecular analysis of ten muscle biopsies from patients with molecularly diagnosed LGMD2I. Hypoglycosylation of α-dystroglycan was observed in all FKRP-mutated patients. Muscle histopathology was consistent with either severe muscular dystrophy or myopathy with a mild inflammatory response consisting of up-regulation of class I major histocompatibility complex in skeletal muscle fibers and small foci of mononuclear cells. At the ultrastructural level, muscle fibers showed focal thinning of basal lamina and swollen endoplasmic reticulum cisternae with membrane re-arrangement. The pathways of the unfolded protein response (UPR; glucose-regulated protein 78 and CHOP) were significantly activated in LGMD2I muscle tissue. Our data suggest that the UPR response is activated in LGMD2I muscle biopsies, and the observed histopathological and ultrastructural alterations may be related to sarcoplasmic structures involved in FKRP and α-dystroglycan metabolism and malfunctioning.

Original languageEnglish
Pages (from-to)1047-1055
Number of pages9
JournalVirchows Archiv
Volume451
Issue number6
DOIs
Publication statusPublished - Dec 2007

Keywords

  • FKRP
  • Glycosylation
  • LGMD2I
  • Muscular dystrophy
  • UPR

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Boito, C. A., Fanin, M., Gavassini, B. F., Cenacchi, G., Angelini, C., & Pegoraro, E. (2007). Biochemical and ultrastructural evidence of endoplasmic reticulum stress in LGMD2I. Virchows Archiv, 451(6), 1047-1055. https://doi.org/10.1007/s00428-007-0515-3