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Clinical signs and neuropathologic abnormalities in working Australian Kelpies with globoid cell leukodystrophy (Krabbe disease)

Citation

Fletcher, JL and Williamson, P and Horan, D and Taylor, RM, Clinical signs and neuropathologic abnormalities in working Australian Kelpies with globoid cell leukodystrophy (Krabbe disease), American Veterinary Medical Association. Journal, 237, (6) pp. 682-688. ISSN 0003-1488 (2010) [Refereed Article]


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DOI: doi:10.2460/javma.237.6.682

Abstract

Objective: To characterize the clinical signs of globoid cell leukodystrophy (GLD) in Australian Kelpies from a working line (AWKs) and determine whether an association existed between these signs and degrees of demyelination and inflammatory responses in affected brains.

Design: Case-control study.

Animals: 4 AWKs with GLD (cases) and 7 unaffected young adult dogs of mixed breeding (controls).

Procedures: Clinical records were reviewed for information on signalment, and samples of neurologic tissues underwent histological processing, immunohistochemical staining, and image analysis. Findings were compared between case and control dogs.

Results: The 4 affected AWKs had progressive ataxia, tremors, and paresis and low leukocyte activity of galactosylceramidase, the lysosomal enzyme deficient in GLD. Image analysis of neurologic tissue revealed globoid cells characteristic of GLD and substantial demyelination in the peripheral and central nervous systems, relative to that in neurologic tissue from control dogs. This was accompanied by microglial activation, reactive astrocyto-sis, and axonal spheroid formation.

Conclusions and clinical relevance: The demyelination, inflammatory responses, and axo-nal spheroids evident in the AWKs were consistent with the clinical signs of peripheral nerve, spinal cord, and cerebellar dysfunction. Because GLD is an autosomal recessive inherited disease, with considerable overlap in galactosylceramidase activity existing among heterozygotes and noncarriers, development of a molecular test is important for preventing the perpetuation of this disease in the Australian Kelpie breed.

Item Details

Item Type:Refereed Article
Keywords:lysosomal storage disease, animal model, demyelinating disease
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Cellular nervous system
Objective Division:Manufacturing
Objective Group:Veterinary pharmaceutical products
Objective Field:Veterinary diagnostics
UTAS Author:Fletcher, JL (Dr Jessica Fletcher)
ID Code:147207
Year Published:2010
Web of Science® Times Cited:8
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-10-19
Last Modified:2021-11-04
Downloads:0

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