Expression of a catalytically inactive transmembrane protein tyrosine phosphatase epsilon (tm-PTP epsilon) delays optic nerve myelination
Abstract
Reversible tyrosine phosphorylation is integral to the process of oligodendrocyte differentiation. To interfere with the subset of the phosphorylation cycle overseen by protein tyrosine phosphatase epsilon (PTP epsilon) in oligodendrocytes, we applied a substrate-trapping approach in the development of transgenic mice overexpressing a catalytically inactive, transmembrane PTP epsilon-hemaglutinin (tm-PTP epsilon-HA) from the dual promoter element of the gene encoding the myelin protein 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). Transgene expression peaked during the active myelinating period, at 2-3 weeks postnatal. Two tyrosine phosphoproteins, alpha-enolase and beta-actin, were phosphorylated to a greater degree in transgenic mice. Despite a high degree of tm-PTP epsilon-HA expression, myelin was grossly normal in nearly all axonal tracts. Phenotypic abnormalities were limited to optic nerve, where a decrease in the degree of myelination was reflected by reduced levels of myelin proteins on postnatal day 21 (PND21), as well as a decrease in the density of differentiated oligodendrocytes. The optic chiasm was reduced in thickness in transgenic mice; optic nerves similarly exhibited a reduction in transverse width. Fur...Continue Reading
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