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Publication : Altered pathological progression of diaphragm and quadriceps muscle in TNF-deficient, dystrophin-deficient mice.

First Author  Spencer MJ Year  2000
Journal  Neuromuscul Disord Volume  10
Issue  8 Pages  612-9
PubMed ID  11053690 Mgi Jnum  J:103113
Mgi Id  MGI:3608471 Doi  10.1016/s0960-8966(00)00160-7
Citation  Spencer MJ, et al. (2000) Altered pathological progression of diaphragm and quadriceps muscle in TNF-deficient, dystrophin-deficient mice. Neuromuscul Disord 10(8):612-9
abstractText  We have previously demonstrated a role for T cells in Duchenne muscular dystrophy (DMD) using the mdx mouse and have shown that T cell killing of dystrophic muscle can occur through perforin-dependent and perforin-independent mechanisms. In this investigation, we explore the possibility that one perforin-independent mechanism utilized by the T cells is cytokine-based killing, specifically by tumor necrosis factor (TNF). We tested this hypothesis by generating mice that are TNF-deficient and dystrophin-deficient (TNF-/mdx). Body mass and muscle mass of the TNF-/mdx mice were significantly less than TNF+/mdx mice at 8 weeks of age. Creatine kinase levels and overall muscle strength were unchanged. Histopathology measurements showed different results in the diaphragm and quadriceps muscles. These data suggest that removal of TNF in vivo in dystrophic mice has differential effects on diaphragm and quadriceps suggesting that TNF is an unfavorable target for immunotherapy for DMD.
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