Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase.

To investigate the role of neurofilaments in motor neuron disease caused by superoxide dismutase (SOD1) mutations, transgenic mice expressing a amyotrophic lateral sclerosis-linked SOD1 mutant (SOD1(G37R)) were mated with transgenic mice expressing human neurofilament heavy (NF-H) subunits. Unexpectedly, expression of human NF-H transgenes increased by up to 65%, the mean lifespan of SOD1(G37R) mice. Microscopic examination corroborated the protective effect of NF-H protein against SOD1 toxicity. Although massive neurodegeneration occurred in 1-yr-old mice expressing SOD1(G37R) alone, spinal root axons and motor neurons were remarkably spared in doubly SOD1(G37R);NF-H-transgenic littermates.