Animal models for motor neuron diseases: research directions.

Animal models of motor neuron diseases fall into three categories, hereditary (e.g., the motor neuron degenerative, wobbler, wasted, and autosomal-recessive progressive motor neuropathy mouse models), sporadically occurring (e.g., equine motor neuron disease), and experimentally induced (e.g., transgenic mice carrying a mutation in the gene encoding human Cu/Zn superoxide dismutase, toxic models) disorders. The models currently have three major drawbacks. First, there is no model imitating the progressive course of human disease with deficits of the upper and lower motor neurons. Second, experimentally induced conditions are based on a hypothesis of the pathogenetic mechanisms of human motor neuron diseases. Motor deficits are usually induced by compounds or agents that represent a single possible pathogenetic mechanism, which reduces the value of the model. Finally, the molecular biology, biochemistry, and neuropathology of the hereditary disorders are ill-defined. Future approaches should minimize the drawbacks of the current models and focus on mechanisms that are part of the etiopathogenesis of the human diseases.