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

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D. / Skedsmo, Fredrik S.; Espenes, Arild; Tranulis, Michael A.; Matiasek, Kaspar; Gunnes, Gjermund; Bjerkås, Inge; Moe, Lars; Røed, Susan Skogtvedt; Berendt, Mette; Fredholm, Merete; Rohdin, Cecilia; Shelton, G. Diane; Bruheim, Per; Stafsnes, Marit H.; Bartosova, Zdenka; Hermansen, Lene C.; Stigen, Øyvind; Jäderlund, Karin H.

I: Neuromuscular Disorders, Bind 31, Nr. 1, 2021, s. 56-68.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Skedsmo, FS, Espenes, A, Tranulis, MA, Matiasek, K, Gunnes, G, Bjerkås, I, Moe, L, Røed, SS, Berendt, M, Fredholm, M, Rohdin, C, Shelton, GD, Bruheim, P, Stafsnes, MH, Bartosova, Z, Hermansen, LC, Stigen, Ø & Jäderlund, KH 2021, 'Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D', Neuromuscular Disorders, bind 31, nr. 1, s. 56-68. https://doi.org/10.1016/j.nmd.2020.11.010

APA

Skedsmo, F. S., Espenes, A., Tranulis, M. A., Matiasek, K., Gunnes, G., Bjerkås, I., Moe, L., Røed, S. S., Berendt, M., Fredholm, M., Rohdin, C., Shelton, G. D., Bruheim, P., Stafsnes, M. H., Bartosova, Z., Hermansen, L. C., Stigen, Ø., & Jäderlund, K. H. (2021). Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D. Neuromuscular Disorders, 31(1), 56-68. https://doi.org/10.1016/j.nmd.2020.11.010

Vancouver

Skedsmo FS, Espenes A, Tranulis MA, Matiasek K, Gunnes G, Bjerkås I o.a. Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D. Neuromuscular Disorders. 2021;31(1):56-68. https://doi.org/10.1016/j.nmd.2020.11.010

Author

Skedsmo, Fredrik S. ; Espenes, Arild ; Tranulis, Michael A. ; Matiasek, Kaspar ; Gunnes, Gjermund ; Bjerkås, Inge ; Moe, Lars ; Røed, Susan Skogtvedt ; Berendt, Mette ; Fredholm, Merete ; Rohdin, Cecilia ; Shelton, G. Diane ; Bruheim, Per ; Stafsnes, Marit H. ; Bartosova, Zdenka ; Hermansen, Lene C. ; Stigen, Øyvind ; Jäderlund, Karin H. / Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D. I: Neuromuscular Disorders. 2021 ; Bind 31, Nr. 1. s. 56-68.

Bibtex

@article{233270738c8941c78a837b5eda63a2ac,
title = "Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D",
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-Marie-Tooth 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.",
keywords = "Alaskan Malamute, Canine, CMT, Greyhound, N-myc downstream-regulated gene 1, Polyneuropathy",
author = "Skedsmo, {Fredrik S.} and Arild Espenes and Tranulis, {Michael A.} and Kaspar Matiasek and Gjermund Gunnes and Inge Bjerk{\aa}s and Lars Moe and R{\o}ed, {Susan Skogtvedt} and Mette Berendt and Merete Fredholm and Cecilia Rohdin and Shelton, {G. Diane} and Per Bruheim and Stafsnes, {Marit H.} and Zdenka Bartosova and Hermansen, {Lene C.} and {\O}yvind Stigen and J{\"a}derlund, {Karin H.}",
year = "2021",
doi = "10.1016/j.nmd.2020.11.010",
language = "English",
volume = "31",
pages = "56--68",
journal = "Journal of Neuromuscular Diseases",
issn = "0960-8966",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D

AU - Skedsmo, Fredrik S.

AU - Espenes, Arild

AU - Tranulis, Michael A.

AU - Matiasek, Kaspar

AU - Gunnes, Gjermund

AU - Bjerkås, Inge

AU - Moe, Lars

AU - Røed, Susan Skogtvedt

AU - Berendt, Mette

AU - Fredholm, Merete

AU - Rohdin, Cecilia

AU - Shelton, G. Diane

AU - Bruheim, Per

AU - Stafsnes, Marit H.

AU - Bartosova, Zdenka

AU - Hermansen, Lene C.

AU - Stigen, Øyvind

AU - Jäderlund, Karin H.

PY - 2021

Y1 - 2021

N2 - 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-Marie-Tooth 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.

AB - 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-Marie-Tooth 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.

KW - Alaskan Malamute

KW - Canine

KW - CMT

KW - Greyhound

KW - N-myc downstream-regulated gene 1

KW - Polyneuropathy

U2 - 10.1016/j.nmd.2020.11.010

DO - 10.1016/j.nmd.2020.11.010

M3 - Journal article

C2 - 33334662

AN - SCOPUS:85097777817

VL - 31

SP - 56

EP - 68

JO - Journal of Neuromuscular Diseases

JF - Journal of Neuromuscular Diseases

SN - 0960-8966

IS - 1

ER -

ID: 254774874