The function of the Periaxin gene during nerve repair in a model of CMT4F.
Mutations in the Periaxin (PRX) gene are known to cause autosomal recessive demyelinating Charcot-Marie-Tooth (CMT4F) and Dejerine-Sottas disease. The pathogenesis of these diseases is not fully understood. However, progress is being made by studying both the periaxin-null mouse, a mouse model of the disease, and the protein-protein interactions of periaxin. L-periaxin is a constituent of the dystroglycan-dystrophin-related protein-2 complex linking the Schwann cell cytoskeleton to the extracellular matrix. Although periaxin-null mice myelinate normally, they develop a demyelinating peripheral neuropathy later in life. This suggests that periaxin is required for the stable maintenance of a normal myelin sheath. We carried out sciatic nerve crushes in 6-week-old periaxin-null mice, and, 6 weeks later, found that although the number of myelinated axons had returned to normal, the axon diameters remained smaller than in the contralateral uncrushed nerve. Not only do periaxin-null mice have more hyper-myelinated axons than their wild-type counterparts but they also recapitulate this hypermyelination during regeneration. Therefore, periaxin-null mice can undergo peripheral nerve remyelination, but the regulation of peripheral myelin thickness is disrupted.
Williams
Anna C
AC
Department of Preclinical Veterinary Sciences, University of Edinburgh, Summerhall, UK.
Brophy
Peter J
PJ
D000818:Animals; D001369:Axons / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D005109:Extracellular Matrix / Q000473:pathology; D017353:Gene Deletion; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009186:Myelin Sheath / Q000473:pathology; D009416:Nerve Regeneration / Q000235:genetics*; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology
D008565:Membrane Proteins; C086745:periaxin