Skip to main content
Open Access Publications from the University of California

A reporter mouse for optical imaging of inflammation in mdx muscles

  • Author(s): Martinez, L
  • Ermolova, NV
  • Ishikawa, TO
  • Stout, DB
  • Herschman, HR
  • Spencer, MJ
  • et al.

© 2015 Martinez et al.; licensee BioMed Central. Background: Duchenne muscular dystrophy (DMD) is due to mutations in the gene coding for human DMD; DMD is characterized by progressive muscle degeneration, inflammation, fat accumulation, and fibrosis. The mdx mouse model of DMD lacks dystrophin protein and undergoes a predictable disease course. While this model has been a valuable resource for pre-clinical studies aiming to test therapeutic compounds, its utility is compromised by a lack of reliable biochemical tools to quantifiably assay muscle disease. Additionally, there are few non-invasive assays available to researchers for measuring early indicators of disease progression in mdx mice. Methods: Mdx mice were crossed to knock-in mice expressing luciferase from the Cox2 promoter. These reporter mice (Cox2 FLuc/+ DMD -/-) were created to serve as a tool for researchers to evaluate muscle inflammation. Luciferase expression was assayed by immunohistochemistry to insure that it correlated with muscle lesions. The luciferase signal was quantified by optical imaging and luciferase assays to verify that the signal correlated with muscle damage. As proof of principle, Cox2 FLuc/+ DMD -/- mice were also treated with prednisolone to validate that a reduction in luciferase signal correlated with prednisone treatment. Results: In this investigation, a novel reporter mouse (Cox2 FLuc/+ DMD -/- mice) was created and validated for non-invasive quantification of muscle inflammation in vivo. In this dystrophic mouse, luciferase is expressed from cyclooxygenase 2 (Cox2) expressing cells and bioluminescence is detected by optical imaging. Bioluminescence is significantly enhanced in damaged muscle of exercised Cox2 FLuc/+ DMD -/- mice compared to non-exercised Cox2 FLuc/+ DMD +/+ mice. Moreover, the Cox2 bioluminescent signal is reduced in Cox2 FLuc/+ DMD -/- mice in response to a course of steroid treatment. Reduction in bioluminescence is detectable prior to measurable therapy-elicited improvements in muscle strength, as assessed by traditional means. Biochemical assay of luciferase provides a second means to quantify muscle inflammation. Conclusions: The Cox2 FLuc/+ DMD -/- mouse is a novel tool to evaluate the therapeutic benefits of drugs intended to target inflammatory aspects of dystrophic pathology. This mouse model will be a useful adjunct to traditional outcome measures in assessing potential therapeutic compounds.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Main Content
Current View