ABSTRACT
Different model systems have helped to gain insights into the pathogenic mechanisms underlying motor neuron death, the hallmark of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and X-linked spinal and bulbar muscular atrophy (SBMA). In 1993, mutations in the superoxide 1 gene (SODl) were discovered that account for 10–20% of familial ALS cases. Knockout mice for these different subunits alone, or double transgenic mice deficient in two Neurofilaments (NF) subunits, did not show a clear phenotype, although in some of these mice a loss of motor axons was detected. The importance of NF content and organization in motor neuron disease is further indicated by crossbreeding experiments of different NF transgenic mice with mutant SOD1 mice. In mice, a motor syndrome was found in transgenic mouse models that contained mutations in proteins playing a role in microtubule structure and/or stability.
