Absence of tumor necrosis factor-alpha does not affect motor neuron disease caused by superoxide dismutase 1 mutations.
An increase in the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) has been observed in patients with amyotrophic lateral sclerosis (ALS) and in the mice models of the disease. TNF-alpha is a potent activator of macrophages and microglia and, under certain conditions, can induce or exacerbate neuronal cell death. Here, we assessed the contribution of TNF-alpha in motor neuron disease in mice overexpressing mutant superoxide dismutase 1 (SOD1) genes linked to familial ALS. This was accomplished by the generation of mice expressing SOD1(G37R) or SOD1(G93A) mutants in the context of TNF-alpha gene knock out. Surprisingly, the absence of TNF-alpha did not affect the lifespan or the extent of motor neuron loss in SOD1 transgenic mice. These results provide compelling evidence indicating that TNF-alpha does not directly contribute to motor neuron degeneration caused by SOD1 mutations.
Gowing
Geneviève
G
Laboratory of Molecular Endocrinology, Centre de Recherche du Centre Hospitalier de l'Université Laval Research Center, Québec, Canada G1V 4G2.
Dequen
Florence
F
Soucy
Geneviève
G
Julien
Jean-Pierre
JP
D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016472:Motor Neuron Disease / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics* / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1