The Absence of Myelin P0 Protein Produces a Novel Molecular Phenotype in Schwann Cell

In order to better understand the pathogenesis of demyelination in P(0) knockout (P(0) -/-) mice, we analyzed the myelin gene expression and the Localization of myelin proteins in P(0) null mouse sciatic nerve. We have demonstrated that the severe demyelinating neuropathy of P(0)-knockout mouse is associated with changes in the program of myelin gene expression. Some changes in myelin gene expression occur early, others occur during adulthood, We also provide evidence that the absence of P(0) is associated with changes in the localization of specific paranodal proteins in the peripheral nerve, These data suggest that P(0) plays an important role, either directly or indirectly, in the program of Schwann cell gene expression and in the specific distribution of peripheral myelin proteins. Furthermore, myelin gene dysregulation and improper localization of paranodal proteins may account, in part, for the pathogenesis of demyelination in P(0)-knockout mice, as well as in human demyelinating peripheral neuropathy associated with mutations in the P(0) gene.