Proceedings of the National Academy of Sciences · 1998 · 209 citations · 40 references
Life SciencesNeurobiologyNeuroscienceMolecular NeurobiologyMolecular NeuroscienceNeurodegenerationAmyotrophic Lateral SclerosisMolecular Basis Of NeurodegenerationMotor Neuron DiseasesNeurodegenerative DiseasesNeurodegenerative DisordersNeuroprotectionAmyotrophic Lateral Sclerosis ModelsGene OverexpressionMicroscopic Neuropathologic ExaminationMotor Neuron Disease ModelsNeurofilament Heavy ChainSod1 PathologySuperoxide Dismutase 1Transgenic Mice
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.
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Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Mark E. Gurney, Haifeng Pu, Arlene Y. Chiu et al. · Science · 1994 · 4.1K citations