Dysmyelination in NCTR-balb/C mouse mutant with a lysosomal storage disorder

A morphological survey of the central nervous system of a NCTR-Balb/C mouse afflicted by neurovisceral storage disease was performed. It has been demonstrated that this mutant is characterized by primary dysmyelination, which is evident as early as 12 days of age. The failure of myelin formation in the CNS was shown by histochemical and ultrastructural methods. Inasmuch as neither lipid-containing macrophages nor infiltrating mononuclear cells were apparent, secondary demyelination could be excluded. The multiform ultrastructural appearance of the storage material in the various CNS cell types suggested heterogeneity of the accumulated substances. The storage materials which reacted positively with periodate-Schiff reagent, but not with other histochemical stains, are most likely the accumulated gangliosides and neutral glycosphingolipids indentified previously in this mutant's brain. Considering the probable role of cholesterol ester in the early phases of myelinogenesis, in conjunction with the fact that the NCTR-Balb/C mouse carries a defect in the esterification of exogenously derived cholesterol, it is possible that the later metabolite is relevant to the impaired myelin formation.