Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/7793
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Type: Journal article
Title: Alpha-mannosidosis in the guinea pig: A new animal model for lysosomal storage disorders
Author: Crawley, A.
Jones, M.
Bonning, L.
Finnie, J.
Hopwood, J.
Citation: Pediatric Research, 1999; 46(5):501-509
Publisher: NATURE PUBLISHING GROUP
Issue Date: 1999
ISSN: 0031-3998
1530-0447
Statement of
Responsibility: 
Allison C Crawley, Margaret Z Jones, Lynda E Bonning, John W Finnie and John J Hopwood
Abstract: Alpha-mannosidosis is a lysosomal storage disorder resulting from deficient activity of lysosomal alpha-mannosidase. It has been described previously in humans, cattle, and cats, and is characterized in all of these species principally by neuronal storage leading to progressive mental deterioration. Two guinea pigs with stunted growth, progressive mental dullness, behavioral abnormalities, and abnormal posture and gait, showed a deficiency of acidic alpha-mannosidase activity in leukocytes, plasma, fibroblasts, and whole liver extracts. Fractionation of liver demonstrated a deficiency of lysosomal (acidic) alpha-mannosidase activity. Thin layer chromatography of urine and tissue extracts confirmed the diagnosis by demonstrating a pattern of excreted and stored oligosaccharides almost identical to that of urine from a human alpha-mannosidosis patient. Widespread neuronal vacuolation was observed throughout the CNS, including the cerebral cortex, hippocampus, thalamus, cerebellum, midbrain, pons, medulla, and the dorsal and ventral horns of the spinal cord. Lysosomal vacuolation also occurred in many other visceral tissues and was particularly severe in pancreas, thyroid, epididymis, and peripheral ganglion. Axonal spheroids were observed in some brain regions, but gliosis and demyelination were not observed. Ultrastructurally, most vacuoles in both the CNS and visceral tissues were lucent or contained fine fibrillar or flocculent material. Rare large neurons in the cerebral cortex contained fine membranous structures. Skeletal abnormalities were very mild. Alpha-mannosidosis in the guinea pig closely resembles the human disease and will provide a convenient model for investigation of new therapeutic strategies for neuronal storage diseases, such as enzyme replacement and gene replacement therapies.
Keywords: Neurons
Vacuoles
Animals
Guinea Pigs
Lysosomal Storage Diseases, Nervous System
alpha-Mannosidosis
Lysosomal Storage Diseases
Disease Models, Animal
Oligosaccharides
Microscopy, Electron
Hematologic Tests
Female
Male
DOI: 10.1203/00006450-199911000-00003
Appears in Collections:Aurora harvest 4
Paediatrics publications

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