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https://hdl.handle.net/2440/7445
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dc.contributor.author | Yogalingam, G. | - |
dc.contributor.author | Hopwood, J. | - |
dc.contributor.author | Crawley, A. | - |
dc.contributor.author | Anson, D. | - |
dc.date.issued | 1998 | - |
dc.identifier.citation | Journal of Biological Chemistry, 1998; 273(22):13421-13429 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.issn | 1083-351X | - |
dc.identifier.uri | http://hdl.handle.net/2440/7445 | - |
dc.description.abstract | The missense mutation, L476P, in the N-acetylgalactosamine 4-sulfatase (4S) gene, has previously been shown to be associated with a severe feline mucopolysaccharidosis type VI (MPS VI) phenotype. The present study describes a second mutation, D520N, in the same MPS VI cat colony, which is inherited independently of L476P and is associated with a clinically mild MPS VI phenotype in D520N/L476P compound heterozygous cats. Biochemical and clinical assessment of L476P homozygous, D520N/L476P compound heterozygous, and D520N homozygous cats demonstrated that the entire range of clinical phenotypes, from severe MPS VI, to mild MPS VI, to normal are clustered within a narrow range of residual 4S activity from 0. 5% to 4.6% of normal levels. When overexpressed in CHO-KI cells, the secreted form of D520N 4S was inactivated in neutral pH conditions. In addition, intracellular D520N 4S protein was rapidly degraded and corresponded to 37%, 14.5%, and 0.67% of normal 4S protein levels in the microsomal, endosomal, and lysosomal compartments, respectively. However, the specific activity of lysosomal D520N 4S was elevated 22. 5-fold when compared with wild-type 4S. These results suggest that the D520N mutation causes a rapid degradation of 4S protein. The effect of this is partially ameliorated as a result of a significant elevation in the specific activity of mutant D520N 4S reaching the lysosomal compartment. | - |
dc.language.iso | en | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.source.uri | http://dx.doi.org/10.1074/jbc.273.22.13421 | - |
dc.subject | CHO Cells | - |
dc.subject | Subcellular Fractions | - |
dc.subject | Fibroblasts | - |
dc.subject | Skin | - |
dc.subject | Animals | - |
dc.subject | Cats | - |
dc.subject | Mucopolysaccharidosis VI | - |
dc.subject | Chondro-4-Sulfatase | - |
dc.subject | Glycosaminoglycans | - |
dc.subject | Endocytosis | - |
dc.subject | Biological Transport | - |
dc.subject | Genotype | - |
dc.subject | Heterozygote | - |
dc.subject | Homozygote | - |
dc.subject | Phenotype | - |
dc.subject | Mutation | - |
dc.subject | Cricetinae | - |
dc.title | Mild feline mucopolysaccharidosis type VI. Identification of an N-acetylgalactosamine-4-sulfatase mutation causing instability and increased specific activity | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1074/jbc.273.22.13421 | - |
pubs.publication-status | Published | - |
Appears in Collections: | Aurora harvest 5 Paediatrics publications |
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