A suspected new canine storage disease

Hartley, W. J.; Canfield, P.J.; Donnelly, Thomas M.

doi:10.1007/bf00690639

Cited by 28 publications

(16 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Progressive formation of storage bodies or vacuoles is a prominent feature of many LSD which is associated with alteration to neuron structure and neuron loss in animal and human models of LSD [3] . Vacuolation was a feature of fucosidosis which developed after birth, a finding which contrasts with formation of storage vacuoles in the foetus of murine and guinea pig animal models for MPS VII and ␣ -mannosidosis, respectively [20][21][22] .…”

Section: Discussionmentioning

confidence: 99%

Canine Fucosidosis: A Neuroprogressive Disorder

Kondagari

Ramanathan²,

Taylor³

2011

Neurodegener Dis

View full text Add to dashboard Cite

The lysosomal storage disease, canine fucosidosis, is caused by the absence of the lysosomal enzyme canine α-L-fucosidase with storage of undegraded fucose-rich material in different organs. Canine fucosidosis is a severe, progressive, fatal neurological disease which results in death or euthanasia and is the only available animal model for this human disease. We analysed the progressive neuropathology from birth to severe clinical disease and related this to the clinical signs. At birth no vacuolation was observed in fucosidosis brain; however, a complex storage presence with vacuolation was well established by 4 months of age, before the clinical signs of motor dysfunction which occurred at 10–12 months of age. Purkinje cell loss, neuronal loss, gliosis, perivascular storage and demyelination accompanied disease progression. Increased vacuolation (15.3-fold increase compared to controls) coincided with advanced motor and mental deterioration in late-stage disease. Significant loss of myelin commenced early, with greatest impact in the cerebellum, and was severe in late disease (1.6- to 1.9-fold decrease) compared to controls (p < 0.05) contributing to clinical signs of motor and mental dysfunction. This detailed description and quantification of the CNS pathology in canine fucosidosis will inform monitoring of the onset, progression and response of this disease to therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Canine Fucosidosis: A Neuroprogressive Disorder

Kondagari

Ramanathan²,

Taylor³

2011

Neurodegener Dis

View full text Add to dashboard Cite

show abstract

“…As in humans, fucosidosis in canines is due to an autosomal recessive enzymatic deficiency of α-L-fucosidase (304) and is the only animal model for the human disease. In dogs, fucosidosis affects English Springer Spaniels and is a severe, progressively fatal neurodegenerative disease (305). Compared to humans, canines show a relative consistency in neurologic clinical signs and pathology.…”

Section: Fucosidosis In Caninesmentioning

confidence: 99%

Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases

et al. 2020

View full text Add to dashboard Cite

Mouse models of human disease remain the bread and butter of modern biology and therapeutic discovery. Nonetheless, more often than not mouse models do not reproduce the pathophysiology of the human conditions they are designed to mimic. Naturally occurring large animal models have predominantly been found in companion animals or livestock because of their emotional or economic value to modern society and, unlike mice, often recapitulate the human disease state. In particular, numerous models have been discovered in dogs and have a fundamental role in bridging proof of concept studies in mice to human clinical trials. The present article is a review that highlights current canine models of human diseases, including Alzheimer's disease, degenerative myelopathy, neuronal ceroid lipofuscinosis, globoid cell leukodystrophy, Duchenne muscular dystrophy, mucopolysaccharidosis, and fucosidosis. The goal of the review is to discuss canine and human neurodegenerative pathophysiologic similarities, introduce the animal models, and shed light on the ability of canine models to facilitate current and future treatment trials.

show abstract

“…The typical clinical findings in canine fucosidosis are motor and mental deterioration in ESS over 18 months of age. Minor variations in the pattern of signs have been reported, for example two dogs in which weight loss was the first sign observed (Hartley, Canfield and Donnelly, 1982;Friend, Barr and Embury, 1985), however the similarity of clinical signs is a distinctive feature of the disease. The animals in this report were clinically normal in the first year of life, developed gait and behavioural deficits before 30 months of age and then progressed, with minor daily variation to severe ataxia, hearing and visual impairment with mental deterioration necessitating euthanasia before 40 months of age.…”

Section: Laboratory Jindingsmentioning

confidence: 99%

Canine fucosidosis: clinical findings

Taylor

Farrow

Healy

1987

J of Small Animal Practice

View full text Add to dashboard Cite

The clinical course of canine fucosidosis, a neurovisceral lysosomal storage disease, is described from observations of 31 affected English Springer Spaniels. The diagnosis of fucosidosis was suggested by the development of multifocal neurological signs in the second year of life and confirmed by a deficiency of alpha‐L‐fucosidase activity in plasma and leucocytes. The progressive motor and mental deterioration was similar in all dogs and no affected animal survived to four years of age. Alpha‐L‐fucosidase activity in plasma was <0·05 μ/1 in all cases. The activity in leucocytes and other tissues was < 5 per cent of that of normal dogs. Vacuolated leucocytes occurred in cerebrospinal fluid, blood and bone marrow. The enlargement of peripheral nerves which is observed at autopsy could be detected by palpation of the ulnar nerve in advanced disease, however the results of electrodiagnostic studies were within normal limits. The clinical signs and pathological changes were found to be remarkably consistent from case to case making it an excellent model for investigating therapeutic strategies in human lysosomal storage disorders.

show abstract

A suspected new canine storage disease

Cited by 28 publications

References 11 publications

Canine Fucosidosis: A Neuroprogressive Disorder

Canine Fucosidosis: A Neuroprogressive Disorder

Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases

Canine fucosidosis: clinical findings

Contact Info

Product

Resources

About