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Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D

Skedsmo, Fredrik S. and Espenes, Arild and Tranulis, Michael A. and Matiasek, Kaspar and Gunnes, Gjermund and Bjerkås, Inge and Moe, Lars and Skogtvedt Røed, Susan and Berendt, Mette and Fredholm, Merete and Rohdin, Cecilia and Shelton, G. Diane and Bruheim, Per and Stafsnes, Marit H. and Bartosova, Zdenka and Stigen, Øyvind and Jäderlund, Karin H. (2021). Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D. Neuromuscular Disorders. 31 , 56-68
[Research article]

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Abstract

Mutations in the N-myc downstream-regulated gene 1 (NDRG1) cause degenerative polyneuropathy in ways that are poorly understood. We have investigated Alaskan Malamute dogs with neuropathy caused by a missense mutation in NDRG1. In affected animals, nerve levels of NDRG1 protein were reduced by more than 70% (p < 0.03). Nerve fibers were thinly myelinated, loss of large myelinated fibers was pronounced and teased fiber preparations showed both demyelination and remyelination. Inclusions of filamentous material containing actin were present in adaxonal Schwann cell cytoplasm and Schmidt-Lanterman clefts. This condition strongly resembles the human Charcot-MarieTooth type 4D. However, the focally folded myelin with adaxonal infoldings segregating the axon found in this study are ultrastructural changes not described in the human disease. Furthermore, lipidomic analysis revealed a profound loss of peripheral nerve lipids. Our data suggest that the low levels of mutant NDRG1 is insufficient to support Schwann cells in maintaining myelin homeostasis. (C) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license.

Authors/Creators:Skedsmo, Fredrik S. and Espenes, Arild and Tranulis, Michael A. and Matiasek, Kaspar and Gunnes, Gjermund and Bjerkås, Inge and Moe, Lars and Skogtvedt Røed, Susan and Berendt, Mette and Fredholm, Merete and Rohdin, Cecilia and Shelton, G. Diane and Bruheim, Per and Stafsnes, Marit H. and Bartosova, Zdenka and Stigen, Øyvind and Jäderlund, Karin H.
Title:Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D
Series Name/Journal:Neuromuscular Disorders
Year of publishing :2021
Volume:31
Page range:56-68
Number of Pages:13
Publisher:PERGAMON-ELSEVIER SCIENCE LTD
ISSN:0960-8966
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Keywords:Alaskan Malamute, Canine, CMT, Greyhound, N-myc downstream-regulated gene 1, Polyneuropathy
URN:NBN:urn:nbn:se:slu:epsilon-p-110635
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-110635
Additional ID:
Type of IDID
DOI10.1016/j.nmd.2020.11.010
Web of Science (WoS)000608362400009
ID Code:23470
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
Deposited By: SLUpub Connector
Deposited On:11 May 2021 11:23
Metadata Last Modified:11 May 2021 11:31

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