Differential vulnerability of cranial motoneurons in mouse models with motor neuron degeneration.

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of selective motoneuron populations, yet it remains unclear why some groups of motoneurons are more vulnerable than others. Our aim was to compare the motoneuron loss in five cranial nuclei at different stages of the disease in three mouse models of ALS: two naturally occurring murine models (progressive motor neuronopathy (pmn) and wobbler) and a transgenic mouse model with a human G93A mutation in the superoxide dismutase-1 (SOD1) gene. By quantifying these different motoneuron populations we report that the degree of degeneration in the various cranial motoneuron nuclei depends on the mouse model and the stage of the disease. The biologically most significant difference between the mutations occurs in the oculomotor/trochlear nucleus which is affected in the pmn mouse but not in the wobbler and SOD G93A mice. These results suggest that there is a selective degeneration of cranial motoneurons in these mouse models as in ALS patients.