13 PTPRJ Fictions Revealed

The g ratio was decreased significantly in the transgene-complemented rumpshaker (rsh 0.789 ?0.007, rshtr 0.753 ?0.01, n = 6; P = 0.035), although both mutants had disproportionately thin sheaths compared with wild type (0.71 ?0.01; Fig. 3C). Insofar as neither the mean axon diameter nor the axon diameter frequency profile differed between the two mutants (data not shown), the change in g ratio indicates that the myelin sheaths were proportionately thicker for a given axon diameter in the presence of the transgene. Additionally, axon diameters did not differ between mutants and wild type. Wild-type myelin had easily identifiable major dense (MDL) and intraperiod (IPL) lines (Fig. 3D), with a periodicity of 11.24 ?0.31 nm, whereas the periodicity of rumpshaker myelin was selleck chemicals 9.96 ?0.13 nm (mean ?SEM; P find more complementation, reaching wild-type levels (Fig. 4B,C). The NAD-dependent deacetylase SirT2 has recently been identified as a significant myelin PTPRJ protein (Roth et al., 2006), and it has been proposed that PLP is involved in its transport to the myelin sheath (Werner et al., 2007). Here we found that, relative to that in wild type, the SirT2 level was reduced in rumpshaker and was restored to wild-type level in transgene-complemented rumpshaker (Fig. 4B). In contrast, MBP was not enhanced by the transgene at this age (Fig. 4B,D). Transgenic complementation increased CNP and MAG, although levels remained lower than wild type (Fig. 4B,D). To determine whether the introduction of the transgene resulted in a redistribution of PLP to intracellular compartments, the membrane-enriched pellet fractions generated during myelin extraction were analyzed. The profiles of PLP/DM20 levels and also MBP levels for each genotype were similar to those observed in the myelin fractions (Supp. Info. Fig. 1). This strongly suggests that there is no significant redistribution. In cultured oligodendrocytes, which do not elaborate a myelin sheath, the transgene also normalized PLP/DM20 levels without a commensurate elevation in MBP (Fig. 4E,F).