Mice hemizygous for this G37R-SOD1 transgene are viable and fertile. The expressed G37R mutant form of human SOD1 is characterized as an enzymatically active, "gain of adverse function" mutation. Hemizygotes develop symptoms and pathology resembling human Amyotrophic Lateral Sclerosis (ALS), with paralyzation in one or more limbs attributable to the loss of motor neurons from the spinal cord. Transgenic mice from the highest expressing founder line (G37R(42) or line 42) express a 14-fold increase in SOD1 activity in spinal cord High expression of G37R-SOD1 is associated with ALS pathology in motor neurons of the spinal cord and brainstem, widespread degenerative changes in other neuronal populations, and mild-to-moderate vacuolar changes in kidney. These high-expressing G37R(42) (or G37R-SOD1 line 42) transgenic mice may be useful in studying neuromuscular disorders, including Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease).
The original publication by Wong et al assessed survival on a mixed genetic background and noted death occurring around 3.5-4 months of age. Since then, this allele has been backcrossed to C57BL/6J and made fully congenic. This change in genetic background has resulted in a change in disease onset and progression. In a study conducted at The Jackson Laboratory involving a cohort of 21 female transgenic mice, it was found that 90% of the animals survived to 25 weeks, 50% survived to 27 weeks, and death occurred in 100% of the mice by 29 weeks. IN SUMMARY: ON A C57BL/6J BACKGROUND SURVIVAL IS INCREASED TO 6-7 MONTHS.
