SummaryThe eye muscles of humans with either inherited or sporadic forms of ALS are relatively unaffected during disease progression, a function of sparing of the cranial nerve motor neurons supplying them. Here we observe that cranial nerve nuclei are also spared in a mouse model of inherited SOD1-linked ALS. We examined the cranial nerve motor nuclei in a mouse strain, G85R SOD1YFP, which carries a high copy transgene encoding a mutant human SOD1-YFP fusion protein, that exhibits florid YFP-fluorescent aggregates in spinal cord motor neurons and paralyzes by 6 months of age. We observed in the cranial nerve nuclei that innervate the eye, 3N (oculomotor), 4N (trochlear), and 6N (abducens), that there was little (4N, 6N) or no (3N) aggregation, in comparison with other motor nuclei, 5N (trigeminal), 7N (facial), and 12N (hypoglossal), in the latter two of which florid aggregation was observed. Correspondingly, the number of ChAT positive motor neurons in 3N of G85R SOD1YFP relative to that in 3N of ChAT-EGFP mice showed that there was no loss of motor neurons over time, whereas in 12N there was progressive loss of motor neurons, amounting to a loss of ∼30% from G85R SOD1YFP by end-stage. Thus, the sparing of extraocular motor neurons as occurs in humans with ALS appears to be replicated in our SOD1-linked ALS mouse strain, supporting the validity of the mouse model for studying this aspect of selective motor system loss in ALS. Comparisons of extraocular motor neurons (e.g., from 3N), resistant to ALS pathology, with other cranial motor neurons (e.g., from 12N), sensitive to such pathology, may thus be of value in understanding mechanisms of protection vs. susceptibility of motor neurons.
Motor nuclei innervating eye muscles spared in mouse model of SOD1-linked ALS
