title: Transforming growth factor beta 1 may regulate the stability of mature myelin sheaths.
abstract: The molecular mechanisms underlying peripheral neuropathies have only been partially elucidated. In particular, the regulatory factors that control the stability and turnover of mature myelin are largely unknown. Transforming growth factor beta 1 (TGF-beta1), and its associated receptors, are expressed by mature Schwann cells. On this basis, we postulated that TGF-beta1 may be an autocrine regulator of mature myelin. This hypothesis was tested by examining the ultrastructure of myelin in adult mice that have a null mutation of their TGF-beta1 gene. We report here that the myelin of these mice is grossly abnormal. At the nodes of Ranvier, the cytoplasmic collars of the Schwann cells were expanded and the myelin had a honeycomb appearance. Focal (tomacula-like) hypermyelin structures were observed in the internodal regions of a significant number of axons in mutant nerve, and were not observed in littermate controls. Axon diameters were within the normal range and no axonal pathology was evident in mutant nerve and macrophages were absent. Results imply that lack of TGF-beta1 may have a direct effect on Schwann cells. We suggest that TGF-beta1 may stabilise compact myelin via an autocrine mechanism.
authors.affiliation: Arizona Research Laboratories, Department of Neuroscience, University of Arizona, Tucson, AZ, USA.
authors.forename: W Antony
authors.initials: WA
authors.lastname: Day
authors.forename: Kyoko
authors.initials: K
authors.lastname: Koishi
authors.forename: Ian S
authors.initials: IS
authors.lastname: McLennan
mesh_terms: D000818:Animals; D007150:Immunohistochemistry; D051379:Mice; D008812:Mice, Hairless; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009154:Mutation; D009186:Myelin Sheath / Q000473:pathology* / Q000648:ultrastructure; D011901:Ranvier's Nodes / Q000473:pathology / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000473:pathology* / Q000648:ultrastructure; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
chemical_list: C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1