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Structural abnormalities and deficient maintenance of peripheral nerve myelin in mice lacking the gap junction
P Anzini1, D H Neuberg, M Schachner
1Department of Neurobiology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
Abstract:
Mutations affecting the connexin 32 (Cx32) gene are associated with the X-linked form of the hereditary peripheral neuropathy Charcot-Marie-Tooth disease (CMTX). We show that Cx32-deficient mice develop a late-onset progressive peripheral neuropathy with abnormalities comparable to those associated with CMTX, thus providing proof of the critical role of Cx32 in the maintenance of peripheral nerve myelin and an animal model for CMTX. Frequently observed features include abnormally thin myelin sheaths, cellular onion bulb formation reflecting myelin degeneration-induced Schwann cell proliferation, and enlarged periaxonal collars while nerve conductance properties are altered only slightly. These observations are consistent with earlier hypotheses suggesting a function of Cx32 as a channel-forming protein that facilitates the communication between the abaxonal and adaxonal aspects of Schwann cell cytoplasm.
Insights
Connexin 32 (Cx32) gene mutations cause X-linked Charcot-Marie-Tooth disease (CMTX). Cx32-deficient mice develop a progressive peripheral neuropathy, confirming Cx32
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Mutations in the connexin 32 (Cx32) gene are linked to Charcot-Marie-Tooth disease type X (CMTX).
- The precise role of Cx32 in peripheral nerve maintenance remains incompletely understood.
Purpose of the Study:
- To investigate the function of Cx32 in peripheral nerve myelination.
- To establish a Cx32-deficient mouse model for studying CMTX pathogenesis.
Main Methods:
- Generation and characterization of Cx32-deficient mice.
- Histological analysis of peripheral nerve morphology.
- Assessment of electrophysiological nerve conduction properties.
Main Results:
- Cx32-deficient mice exhibit late-onset, progressive peripheral neuropathy.
- Abnormalities include thin myelin sheaths, Schwann cell proliferation (onion bulbs), and enlarged periaxonal collars.
- Nerve conduction velocities are only slightly altered, suggesting a primary role in myelin maintenance rather than rapid signal transmission.
Conclusions:
- Cx32 is critical for the maintenance of peripheral nerve myelin.
- Cx32 deficiency leads to neuropathic changes mimicking CMTX.
- The findings support Cx32's role as a channel protein facilitating Schwann cell communication.