Retardation of fast axonal transport in wobbler mice

To investigate axonal function in a model of early motor neuron disease, we examined fast and slow components of anterograde axonal transport in the less-affected hindlimb motor neurons of wobbler mice. To study the fast component (FC), we injected tritiated amino acids into the lumbar spinal cord and retrieved the sciatic nerve after 2 or 3 h. The transport distance was the extent of the plateau of labeling; regression analysis indicated that FC was 25% slower in wobbler mice than in unaffected littermates (P < 0.01). To study slow component (SC), [35S]methionine was injected. Transport distances were to the peaks of labeling for structural proteins after 2 or 3 weeks. Rates for each subcomponent (SCa and SCb) were unaffected by wobbler disease. Because the rate of retrograde FC is also unaffected (Mitsumoto et al., Muscle & Nerve 13:121-126, 1990), we conclude that wobbler disease specifically retards anterograde FC in less-affected hindlimb motor neurons, whereas all components of axonal transport are retarded in forelimb motor neurons.