Humanization of skeletal muscle innervation to study ALS

ALS is a motoneuron neurodegenerative disease that predominantly effects elderly people. Most in vivo and in vitro studies studying ALS either use models that die early in life or use tissue culture (i.e. human induced pluripotent stem cell-derived motoneurons; iPSCMNs). In vitro human iPSCM studies typically examine iPSCMNs from patents with ALS when they are still immature because they do not live for a long time in culture. This application proposed using a human iPSCMN/mouse chimeric model to examine long-term changes in cell survival and neuromuscular function. The proposal will include young and aged animals to study age differences in this disease.