Mouse Models of Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal disease in which degeneration of upper and lower motor neurons leads to progressive muscle weakness. The most common form of adult motor neuron disease in humans, ALS typically initiates in middle to late life, leading to paralysis and death within 3-5 years. Approximately 10% of ALS cases are inherited in an autosomal dominant fashion. These familial ALS (FALS) cases are generally thought to be clinically indistinguishable from sporadic ALS (Emery and Holloway, 1983; Li et al., 1988), although there are exceptions (see later). The disease usually begins asymmetrically in one limb, most commonly the leg, and then appears to spread to involve contiguous groups of motor neurons. Many affected neurons in ALS patients show cytoskeletal pathology in the form of neurofilament accumulations, both within the cell bodies and in proximal axons (Emery and Holloway, 1983; Chou and Fakadej, 1971; Hirano et al., 1984a, Hirano et al., 1984b). Motor neuron loss is also accompanied by reactive gliosis (Leigh et al., 1991), ubiquitin-positive inclusions (Leigh et al., 1991), and apparent fragmentation of the Golgi (Gonatas et al., 1992).