β-Mannosidosis mice: a model for the human lysosomal storage disease
| Autor: | Kathryn L. Lovell, Mei Zhu, Elizabeth D. Hughes, Thomas L. Saunders, Karen H. Friderici, Jon S. Patterson |
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| Rok vydání: | 2005 |
| Předmět: |
Central Nervous System
Male Alpha-mannosidosis Thyroid Gland Oligosaccharides Biology Kidney Mannosidosis Mice Genetics medicine Lysosomal storage disease Animals Humans Molecular Biology Genetics (clinical) Epididymis Mice Knockout chemistry.chemical_classification beta-Mannosidase Kidney metabolism Glycoproteinosis General Medicine beta-Mannosidosis medicine.disease Cell biology Mice Inbred C57BL Disease Models Animal Liver Biochemistry chemistry Gene Targeting Knockout mouse Lysosomes Glycoprotein Cytoplasmic Vacuolation |
| Zdroj: | Human Molecular Genetics. 15:493-500 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddi465 |
| Popis: | Beta-mannosidase, a lysosomal enzyme which acts exclusively at the last step of oligosaccharide catabolism in glycoprotein degradation, functions to cleave the unique beta-linked mannose sugar found in all N-linked oligosaccharides of glycoproteins. Deficiency of this enzyme results in beta-mannosidosis, a lysosomal storage disease characterized by the cellular accumulation of small oligosaccharides. In human beta-mannosidosis, the clinical presentation is variable and can be mild, even when caused by functionally null mutations. In contrast, two existing ruminant animal models have disease that is consistent and severe. To further explore the molecular pathology of this disease and to investigate potential treatment strategies, we produced a beta-mannosidase knockout mouse. Homozygous mutant mice have undetectable beta-mannosidase activity. General appearance and growth of the knockout mice are similar to the wild-type littermates. At >1 year of age, these mice exhibit no dysmorphology or overt neurological problems. The mutant animals have consistent cytoplasmic vacuolation in the central nervous system and minimal vacuolation in most visceral organs. Thin-layer chromatography demonstrated an accumulation of disaccharide in epididymis and brain. This mouse model closely resembles human beta-mannosidosis and provides a useful tool for studying the phenotypic variation in different species and will facilitate the study of potential therapies for lysosomal storage diseases. |
| Databáze: | OpenAIRE |
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