Assessing the role of immuno-proteasomes in a mouse model of familial ALS

The accumulation of protein aggregates is thought to bean important component in the pathogenesis of mutant SOD I -induced disease. Mutant SOD I aggregates appear to be cleared by proteasomes, at least in vitro, suggesting a potentially important role for proteasome degradation pathways in vivo. G93A SOD I transgenic mice show an increase in proteasorne activity and induction of immuno-proteasome subunits within spinal cord as they develop neurological symptoms. To determine what role immuno-proteasomes may have in mutant SOD I -induced disease, we crossed G93A SOD1 transgenic mice with LMP2-/- mice to obtain G93A SOD1 mice lacking the LMP2 immuno-proteasorne subunit. G93A SOD1/LMP2-/-mice show significant reductions in proteasorne function within spinal cord compared to G93A SOD1 mice. However, G93A SOD1 /LM P2-/-mice show no change in motor function decline, or survival compared to G93A SOD I mice. These results indicate that the loss of immuno-proteasorne function in vivo does not significantly alter mutant SOD I -induced disease. (C) 2007 Elsevier Inc. All rights reserved.