Noninvasive imaging of in vivo MuRF1 expression during muscle atrophy

PLoS One. 2014 Apr 7;9(4):e94032. doi: 10.1371/journal.pone.0094032. eCollection 2014.

Abstract

Numerous human diseases can lead to atrophy of skeletal muscle, and loss of this tissue has been correlated with increased mortality and morbidity rates. Clinically addressing muscle atrophy remains an unmet medical need, and the development of preclinical tools to assist drug discovery and basic research in this effort is important for advancing this goal. In this report, we describe the development of a bioluminescent gene reporter rat, based on the zinc finger nuclease-targeted insertion of a bicistronic luciferase reporter into the 3' untranslated region of a muscle specific E3 ubiquitin ligase gene, MuRF1 (Trim63). In longitudinal studies, we noninvasively assess atrophy-related expression of this reporter in three distinct models of muscle loss (sciatic denervation, hindlimb unloading and dexamethasone-treatment) and show that these animals are capable of generating refined detail on in vivo MuRF1 expression with high temporal and anatomical resolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Genes, Reporter
  • Hindlimb Suspension
  • Luminescent Measurements / methods*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / genetics
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / pathology
  • Rats
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Muscle Proteins
  • Tripartite Motif Proteins
  • Trim63 protein, rat
  • Ubiquitin-Protein Ligases

Grants and funding

Financial support for this work was provided by Rigel Pharmaceuticals Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.