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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.

A reporter mouse for optical imaging of inflammation in mdx muscles