16. Drosophila and Mouse Models of Hereditary Myopathy Caused by Mutations in VCP/p97

  1. Valerie Askanas MD, PhD and
  2. W. King Engel MD
  1. Nisha M. Badders and
  2. J. Paul Taylor

Published Online: 19 DEC 2011

DOI: 10.1002/9781444398311.ch16

Muscle Aging, Inclusion-Body Myositis and Myopathies

Muscle Aging, Inclusion-Body Myositis and Myopathies

How to Cite

Badders, N. M. and Taylor, J. P. (2012) Drosophila and Mouse Models of Hereditary Myopathy Caused by Mutations in VCP/p97, in Muscle Aging, Inclusion-Body Myositis and Myopathies (eds V. Askanas and W. K. Engel), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444398311.ch16

Editor Information

  1. Departments of Neurology and Pathology, University of Southern California Neuromuscular Center, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA, USA

Author Information

  1. Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA

Publication History

  1. Published Online: 19 DEC 2011
  2. Published Print: 27 JAN 2012

ISBN Information

Print ISBN: 9781405196468

Online ISBN: 9781444398311

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Keywords:

  • IBMPFD;
  • inclusion-body myopathy;
  • inclusion-body myopathy associated with Paget disease of the bone and frontotemporal dementia;
  • valosin-containing protein;
  • VCP

Summary

Mutations in the gene encoding valosin-containing protein (VCP/p97) lead to a multisystem degenerative disease affecting muscle, central nervous system, and bone (OMIM #167320). Muscle is the most frequently affected tissue, with about 90% of individuals with pathogenic mutations in VCP/p97 experiencing progressive vacuolar myopathy. Muscle pathology in these individuals is characterized by features consistent with inclusion-body myopathy including rimmed vacuoles, ubiquitin-positive TAR DNA-binding protein 43 (TDP-43) accumulation in the sarcoplasm, and inflammatory infiltrate. VCP/p97 is a highly conserved AAA+ ATPase that regulates a wide array of cellular processes. The mechanism whereby mutations in VCP/p97 lead to disease is unknown. Here we describe the development and characterization of fruit fly and mouse models of VCP/p97-related disease. These models represent valuable tools for investigating the molecular pathogenesis and evaluating candidate therapeutics for hereditary inclusion-body myopathy and perhaps for sporadic inclusion-body myositis as well.