The absence of myelin P₀ protein produces a novel molecular phenotype in Schwann cells

In order to better understand the pathogenesis of demyelination in P₀ knockout (P₀ -/-) mice, we analyzed the myelin gene expression and the localization of myelin proteins in P₀ null mouse sciatic nerve. We have demonstrated that the severe demyelinating neuropathy of P₀-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 P₀ is associated with changes in the localization of specific paranodal proteins in the peripheral nerve. These data suggest that P₀ 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 P₀-knockout mice, as well as in human demyelinating peripheral neuropathy associated with mutations in the P₀ gene.