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Glia. 2012 Oct;60(10):1518-28. doi: 10.1002/glia.22371. Epub 2012 Jun 21.

LITAF (SIMPLE) regulates Wallerian degeneration after injury but is not essential for peripheral nerve development and maintenance: implications for Charcot-Marie-Tooth disease.

Author information

1
Department of Biology, Institute of Molecular Health Sciences, Cell Biology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland.

Abstract

Missense mutations affecting the LITAF gene (also known as SIMPLE) lead to the dominantly inherited peripheral neuropathy Charcot-Marie-Tooth disease type 1C (CMT1C). In this study, we sought to determine the requirement of Litaf function in peripheral nerves, the only known affected tissue in CMT1C. We reasoned that this knowledge is a prerequisite for a thorough understanding of the underlying disease mechanism with regard to potential contributions by Litaf loss of function. In addition, we anticipated to obtain valuable information about the basic function of the Litaf protein in peripheral nerves. To address these issues, we generated mice without Litaf expression using gene disruption in embryonic stem cells and analyzed Litaf-deficient peripheral nerves during development, in maintenance, and after injury. Our results show that Litaf function is not absolutely required for peripheral nerve development and maintenance. In injured nerves, however, we found that lack of Litaf led to increased numbers of macrophages during Wallerian degeneration, accelerated myelin destruction, and the emergence of more axonal sprouts. Consistent with these data, the migration of Litaf-deficient macrophages was increased upon chemokine stimulation. We conclude that loss of Litaf function is unlikely to be a major contributor to CMT1C, but modulating effects of macrophages need to be considered in the etiology of the disease.

PMID:
22729949
DOI:
10.1002/glia.22371
[Indexed for MEDLINE]

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