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57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

P104L Caveolin-3 transgenic mice displays signs of endoplasmic reticulum stress

Meeting Abstract

  • presenting/speaker Eva Brauers - Universitätsklinikum Aachen, Institut für Neuropathologie, Aachen, Germany
  • Andreas Roos - Universitätsklinikum Aachen, Institut für Neuropathologie, Aachen, Germany
  • Stephan Buchkremer - Universitätsklinikum Aachen, Institut für Neuropathologie, Aachen, Germany
  • Yoshihide Sunada - Kawasaki Medical School, Department of Neurology, Okayama, Japan
  • Joachim Weis - Universitätsklinikum Aachen, Institut für Neuropathologie, Aachen, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnOP08

DOI: 10.3205/12dgnn008, URN: urn:nbn:de:0183-12dgnn0085

Published: September 11, 2012

© 2012 Brauers et al.
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Outline

Text

Mutations in Caveolin-3, which is mainly expressed in muscle cells, cause autosomal dominant myopathies of different severity ranging from asymptomatic hyperCKemia to lethal LGMD-1C and cardiomyopathy. The molecular pathogenesis of caveolin-3-related muscular disorders is still largely unknown. Previously, we have shown that patients with R26Q and G55S caveolin-3 mutations develop perinuclear vacuoles which are signs of autophagy and endoplasmic reticulum (ER) stress response. Here we correlate our muscle biopsy findings to the P104L mutant caveolin-3 transgenic mouse model for LGMD-1C. WB assays for the mouse model had already suggested a potential effect of the mutation on the ER stress response (Kuga et al., Hum Mol Genet 2011). In our electron microscopy studies we found peculiar alterations of the nuclear envelope with invaginations reminiscent of myonuclear degeneration in Marinesco-Sjögren syndrome (MSS), a neuromuscular disorder due to mutations in the ER protein Sil1. In association with the degenerated nuclei we found vacuolar structures that often contained membranous structures, indicating autophagy. Ongoing functional studies are focussed on the interaction of mutated Caveolin-3 with further proteins involved in the ER stress response, and more specifically, Sil1 function.