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

Paul T. Golumbek, Richard M. Keeling, Anne M. Connolly

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish
Pages (from-to)376-384
Number of pages9
JournalNeuromuscular Disorders
Volume17
Issue number5
DOIs
StatePublished - May 2007

Keywords

  • B-cell
  • Fatigue
  • Immunoglobulin
  • Prednisolone
  • RAG2 knockout
  • Strength
  • T-cell
  • Voluntary wheel running
  • mdx mouse

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