Characterization of a novel SOD-1(G93A) transgenic mouse line with very decelerated disease development.

Amyotrophic Lateral Sclerosis (ALS) is a fatal motoneuron disease, characterized by progressive weakness, muscle wasting and death ensuing 3-5 years after diagnosis. The etiology of ALS is complex and therapeutic approaches rely mostly on transgenic animal models with SOD-1 mutations. Most frequently employed is a mouse line transgenic for SOD-1 (SOD-1 Tg) that contains a point mutation at amino acid position 93 (G->A), present in patients suffering from a familial form of amyotrophic lateral sclerosis. Here we report on a SOD-1 (G93A) Tg mouse line with abnormally delayed onset of disease and prolonged survival. This phenotype arose spontaneously in our colony of the classic SOD-1 (G93A) line. We found that the copy number of the SOD-1 transgene was drastically decreased. We established a new breeding colony, the SOD-1 (G93A)(PS) line (PS for prolonged survival) where the phenotype is stably inherited for 4 generations now. The mice develop symptoms at an age of approximately 12 months and die at 15 months of age. The delayed development of disease may more closely mimic human pathophysiology, and studying drug effects in this model may yield added confidence for potential efficacy of ALS drug candidates.