The WldS gene modestly prolongs survival in the SOD1G93A fALS mouse.

ABSTRACT

The "slow Wallerian degeneration" (Wld(S)) gene is neuroprotective in numerous models of axonal degeneration. Axonal degeneration is an early feature of disease progression in the SOD1G93A mouse, a widely used model of familial amyotrophic lateral sclerosis (fALS). We crossed the Wld(S) mouse with the SOD1G93A mouse to investigate whether the Wld(S) gene could prolong survival and modify neuropathology in these mice. SOD/Wld(S) mice showed levels of motor axon loss similar to that seen in SOD1G93A mice. The presence of the Wld(S) gene, however, modestly prolonged survival and delayed denervation at the neuromuscular junction. Prolonged survival was more prominent in female mice and did not depend on whether animals were heterozygous or homozygous for the Wld(S) gene. We also report that SOD1G93A mice show significant degeneration of sensory axons during the course of disease, supporting previous data from humans demonstrating that ALS is not purely a motor disorder.