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.
Menichella
D M
DM
Institute of Neurology, University of Milan, IRCCS Ospedale Maggiore Policlinico, Italy.
Xu
W
W
Jiang
H
H
Sohi
J
J
Vallat
J M
JM
Baron
P
P
Kamholz
J
J
Shy
M
M
D000818:Animals; D015820:Cadherins / Q000235:genetics; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018993:Myelin P0 Protein / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D012583:Schwann Cells / Q000473:pathology / Q000502:physiology*; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D018993:Myelin P0 Protein; D015534:Trans-Activators; D051176:beta Catenin