These Sod1D83G ENU-induced mutant mice possess a missense mutation in exon 3 of the superoxide dismutase 1 (Sod1) gene. SOD1 is a widely expressed isozyme responsible for destroying free superoxide radicals. SOD1 mutations, including SOD1*D83G, are known to cause Lou Gehrig's disease (Amyotrophic lateral sclerosis; ALS)/motor neuron disease (MND). These mutant mice produce the same mRNA levels as wildtype mice but contain decreased amounts of mutant SOD1 protein, leading to a dose dependant decrease in dismuatase activity. Homozygotes mice are not produced in a Mendelian ratio. They develop a degeneration of the lower and upper motor neurons between 6 and 15 weeks of age. This neuronal cell death ceases in adulthood and the mice do not become paralyzed. However, motor ability continues to deteriorate after 15 weeks of age in homozygous mutants. . This motor dysfunction is underlined by a progressive distal denervation of the neuromuscular junctions of the extensor digitorum longus hindlimb muscle between 15 and 52 weeks of age, leading to progressive peripheral neuropathy. These mice have a reduced life span, and they develop liver tumors, tremors, reduced pelvic elevation, significant sensory deficits. Heterozygotes are viable and fertile, and have a phenotype similar to wildtype littermates, except for in cage motor ability.
