TNF alpha receptor genotype influences smoking-induced muscle-fibre-type shift and atrophy in mice

Acta Neuropathol. 2008 Jun;115(6):675-81. doi: 10.1007/s00401-008-0348-4. Epub 2008 Feb 29.


Systemic manifestations of chronic obstructive pulmonary disease (COPD) include muscle wasting, and tumour necrosis factor alpha (TNFalpha) could represent a major inducer of these processes. We studied skeletal muscle histology in a murine model of cigarette smoke (CS)-induced COPD, comparing mice with different TNFalpha receptor genotypes. Muscles from hind limbs of wild type (WT), TNFalpha receptor 1 knockout (TNF alpha R1KO) and TNF alpha R2KO mice were prepared and weighed. The lower body weight, which was observed in CS-exposed WT and TNF alpha R1KO mice, was paralleled by reduced weights of gastrocnemius and biceps femoris muscle. The gastrocnemius muscle was evaluated for muscle fibre apoptosis and atrophy, and fibre-type distribution. CS-induced apoptosis was observed in all genotypes, while a significant reduction of cross-sectional areas of myofibres was present only in TNF alpha R2KO mice. A CS-induced fibre-type shift from the IIa to the IIb phenotype was observed in WT mice, an increase of muscle-fibre-type IIx was noticed in CS-exposed TNF alpha R2KO mice. Our data suggest that the skeletal muscle manifestations associated with this murine COPD model are under complex regulation by both TNFalpha receptors, but that TNF alpha R2 may be the most important determinant for the outcome of CS-induced myofibre apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Disease Models, Animal
  • Genotype
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Fibers, Skeletal / pathology*
  • Muscle, Skeletal
  • Muscular Atrophy* / genetics
  • Muscular Atrophy* / metabolism
  • Muscular Atrophy* / pathology
  • Organ Size / genetics
  • Pulmonary Disease, Chronic Obstructive* / etiology
  • Pulmonary Disease, Chronic Obstructive* / pathology
  • Pulmonary Disease, Chronic Obstructive* / physiopathology
  • Receptors, Tumor Necrosis Factor, Type I / deficiency
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Receptors, Tumor Necrosis Factor, Type II / deficiency
  • Receptors, Tumor Necrosis Factor, Type II / genetics*
  • Smoking / adverse effects*


  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II