Strength and corticosteroid responsiveness of mdx mice is unchanged by RAG2 gene knockout

Abstract

Corticosteroids improve muscle function in boys with Duchenne muscular dystrophy and mdx mice possibly via effects on T-cell and B-cells. We quantified T-cell/B-cell functional effects and refined prednisolone’s therapeutic mechanism in mdx mice. RAG2 −/− mice, which produce no T-cells or B-cells, were crossed with mdx mice, which lack dystrophin protein. Strength testing (3–36 weeks) was performed on treated and control groups of male mdx RAG2 −/−and mdx RAG2 +/− mice. Longitudinal grip strength testing and hanging wire testing were assessed. Voluntary wheel running and creatine kinase level were measured. The absence of T-cells/B-cells ( RAG2 − /− mutation) caused no physiologic improvement. Prednisolone improved performance in mdx mice, independent of RAG2 gene expression (+ or −/−). Prednisolone treatment increased the frequency of muscle calcification, while RAG2 genotype had no effect. There was no change in fiber type proportions due to RAG2 genotype or prednisolone treatment. Thus, T-cells and/or B-cells (and immunoglobulins), while demonstrable in mdx mouse muscle, are playing a negligible role in their mdx-related functional outcome. Prednisolone’s therapeutic effect is through T-cell/B-cell independent mechanisms in mdx mice.