title: Sox10 is required for Schwann-cell homeostasis and myelin maintenance in the adult peripheral nerve.
abstract: The transcription factor Sox10 functions during multiple consecutive stages of Schwann-cell development in the peripheral nervous system (PNS). Although Sox10 continues to be expressed in mature Schwann cells of the adult peripheral nerve, it is currently unclear whether it is still functional. Here, we used a genetic strategy to selectively delete Sox10 in glia of adult mice in a tamoxifen-dependent manner. The tamoxifen-treated mice developed a severe peripheral neuropathy that was associated with dramatic alterations in peripheral nerve structure and function. Demyelination and axonal degeneration were as much evident as signs of neuroinflammation. Compound action potentials exhibited pathophysiological alterations. Sox10-deleted Schwann cells persisted in the peripheral nerve, but did not exhibit a mature, myelinating phenotype arguing that Sox10 is rather required for differentiation and maintenance of the differentiated state than for survival. Our report is the first evidence that Sox10 is still essentially required for Schwann-cell function in the adult PNS and establishes a useful model in which to study human peripheral neuropathies.
authors.affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bremer
authors.forename: Franziska
authors.initials: F
authors.lastname: Fröb
authors.forename: Tatjana
authors.initials: T
authors.lastname: Kichko
authors.forename: Peter
authors.initials: P
authors.lastname: Reeh
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
authors.forename: Ueli
authors.initials: U
authors.lastname: Suter
authors.forename: Michael
authors.initials: M
authors.lastname: Wegner
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D004965:Estrogen Antagonists / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics*; D020287:In Situ Nick-End Labeling / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D004676:Myelin Basic Protein / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism*; D009431:Neural Conduction / Q000187:drug effects / Q000235:genetics; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000172:deficiency / Q000502:physiology*; D012583:Schwann Cells / Q000502:physiology*; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D013629:Tamoxifen / Q000633:toxicity; D013997:Time Factors
chemical_list: D017252:CD3 Complex; D004965:Estrogen Antagonists; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D013629:Tamoxifen