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.
Copyright © 2011 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Action Potentials / genetics
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Animals
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CD3 Complex / metabolism
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Cell Death / drug effects
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Cell Death / genetics
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Cell Proliferation / drug effects
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Estrogen Antagonists / toxicity
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Homeostasis / drug effects
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Homeostasis / genetics*
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In Situ Nick-End Labeling / methods
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microscopy, Electron, Transmission / methods
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Myelin Basic Protein / metabolism
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Myelin Proteolipid Protein / genetics
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Myelin Sheath / metabolism*
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Neural Conduction / drug effects
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Neural Conduction / genetics
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Peripheral Nervous System Diseases / chemically induced
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Peripheral Nervous System Diseases / pathology*
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Peripheral Nervous System Diseases / physiopathology*
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Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
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SOXE Transcription Factors / deficiency
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SOXE Transcription Factors / physiology*
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Schwann Cells / physiology*
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Sciatic Nerve / metabolism
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Sciatic Nerve / pathology
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Sciatic Nerve / ultrastructure
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Tamoxifen / toxicity
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Time Factors
Substances
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CD3 Complex
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Estrogen Antagonists
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Myelin Basic Protein
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Myelin Proteolipid Protein
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Platelet Endothelial Cell Adhesion Molecule-1
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SOXE Transcription Factors
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Sox10 protein, mouse
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Tamoxifen