Caprine Mucopolysaccharidosis-IIID
| Autor: | Kent Johnson, Philip J. Boyer, Shyh Shyurng Liour, John J. Hopwood, Robert A. Leedle, Beverly A. L. Levene, Douglas A. Gage, P. Sharp, Margaret Z. Jones, Ralph S. Common, J. A. Render, Rebecca E. Lucas, Kevin T. Cavanagh, Joseph Alroy, Joseph Vorro, Heidi M. Hoard, Charles T. Lowrie |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
Pathology medicine.medical_specialty Mucopolysaccharidosis Nonsense mutation Neuraminidase Biology Muscle Smooth Vascular Pathology and Forensic Medicine Glycosaminoglycan Mucopolysaccharidosis III Cellular and Molecular Neuroscience chemistry.chemical_compound Renal Artery Gangliosides Lysosomal storage disease medicine Animals Humans Point Mutation skin and connective tissue diseases Glycosaminoglycans Sanfilippo syndrome Cerebral Cortex Neurons Goat Diseases Goats Myocardium Brain General Medicine Heparan sulfate medicine.disease Immunohistochemistry Animals Newborn Liver Spinal Cord Neurology chemistry Female Endothelium Vascular Heparitin Sulfate Neurology (clinical) Sulfatases |
| Zdroj: | Journal of Neuropathology and Experimental Neurology. 57:148-157 |
| ISSN: | 0022-3069 |
| DOI: | 10.1097/00005072-199802000-00006 |
| Popis: | Several animal models have been developed for the mucopolysaccharidoses (MPSs), a group of lysosomal storage disorders caused by lysosomal hydrolase deficiencies that disrupt the catabolism of glycosaminoglycans (GAG). Among the MPS, the MPS-III (Sanfilippo) syndromes lacked an animal counterpart until recently. In this investigation of caprine MPS-IIID, the clinical, biochemical, morphological, and immunohistochemical studies revealed severe and mild phenotypes like those observed in human MPS III syndromes. Both forms of caprine MPS IIID result from a nonsense mutation and consequent deficiency of lysosomal N-acetylglucosamine 6-sulfatase (G6S) activity and are associated with tissue storage and urinary excretion of heparan sulfate (HS). Using special stains, immunohistochemistry, and electron microscopy, secondary lysosomes filled with GAG were identified in most tissues from affected goats. Primary neuronal accumulation of HS and the secondary storage of gangliosides were observed in the central nervous system (CNS) of these animals. In addition, morphological changes in the CNS such as neuritic expansions and other neuronal alterations that may have functional significance were also seen. The spectrum of lesions was greater in the severe form of caprine MPS IIID and included mild cartilaginous, bony, and corneal lesions. The more pronounced neurological deficits in the severe form were partly related to a greater extent of CNS dysmyelination. These findings demonstrate that caprine MPS IIID is a suitable animal model for the investigation of therapeutic strategies for MPS III syndromes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|