Circulating serum CK level vs. muscle impairment for in situ monitoring burden ofdiseaseinMdx-mice.

Abstract

Duchenne muscular dystrophy (DMD) consists of alack in the expression of the subsarcolemmal protein dystrophin causing progressive muscle dysfunction. Among the widely applied animal models in DMD research is the C57BL/1010ScSn-Dmdmdx mouse, commonly referred to as the "mdx mouse". The potential benefit of novel interventions in this model is often assessed by variables such as functional improvement, histological changes, and creatine kinase (CK) serum levels as an indicator for the extent of in situ muscle damage. Our objective was to determine to what extent the serum CK-level serves asurrogate for muscle dysfunction. In this trial mdx mice were subjected to afour-limb wire-hanging test (WHT) to assess the physical performance as areference for muscle function. As CK is acomponent of the muscle fiber cytosol, its serum activity is supposed to positively correlate with progressing muscle damage. Hence serum CK levels were measured to detect the degree of muscle impairment. The functional tests and the serum CK levels were analyzed for their specific correlation. Although physical performance decreased during the course of the experiment, latency to fall times in the WHT did not correlate with the CK level in mdx mice. Our data suggests that the serum CK activity might be acritical parameter to monitor the progression of muscle impairment in mdx mice. Further this study emphasizes the complexity of the DMD phenotype in the mdx mouse, and the care with which isolated parameters in this model should be interpreted.