Peer-reviewed veterinary case report
Nerve damage from NDRG1 gene mutation in Alaskan Malamute dogs
By Skedsmo, Fredrik S et al.·Published in Neuromuscular disorders : NMD·2021·Department of Companion Animal Clinical Sciences·View original on PubMed →
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Original publication title: Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D.
- Species:
- dog
Plain-English summary
A group of Alaskan Malamute dogs with a genetic mutation were found to have nerve problems that caused weakness and difficulty walking. The affected dogs had significantly reduced levels of a protein called NDRG1, which is important for nerve health. This led to damage in the protective myelin covering their nerves, resulting in symptoms similar to a human condition known as Charcot-Marie-Tooth disease. Unfortunately, the dogs did not recover, as the low levels of the mutated protein were not enough to support the health of their nerves.
People also search for: Alaskan Malamute nerve problems · dog weakness walking · Charcot-Marie-Tooth disease in dogs
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.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/33334662/