Abnormal expression of neurofilament proteins in dysmyelinating axons located in the central nervous system of jimpy mutant mice

Myelination in the peripheral nervous system is considered to increase the phosphorylation level of neurofilament proteins in the axon, resulting in a n increase in axonal calibre. To understand the relationship between myelin ation and neurofilament proteins in axons, we examined jimpy mutant mice wi th a point mutation in the proteolipid protein gene and dysmyelination in t he central nervous system. The jimpy mice exhibited a characteristic simila rity in neurofilament nature to the myelin-deficient mice in the peripheral nervous system reported previously. The following novel results were obtai ned in the jimpy mice: dysmyelinated axons, in which the amount of non-phos phorylated neurofilament-H was drastically increased without a significant reduction of the phosphorylated form, compared with the control myelinated axons, did not suffer any decrease in their diameters. Expression levels of all neurofilament subunit proteins and their mRNAs were enhanced in the ce ntral nervous system tissue. Because the above biochemical data were obtain ed from the cytoskeletal fraction, at least some of the increased neurofila ment-H and -M proteins appeared to be coassembled into neurofilaments but r emained non-phosphorylated, Axonal neurofilaments of the jimpy were, probab ly due to this abnormal stoichiometry and phosphorylation state in neurofil aments, more compact and random in alignment with less prominent cross-brid ges than those of the control, providing possible evidence for disturbing t he axonal transport of other organelles. These results suggest that myelina tion regulates both the expression and phosphorylation of neurofilament pro teins, and is essential for the cytoplasmic organization of myelinated axon s.