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https://hdl.handle.net/2440/7447
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Type: | Journal article |
Title: | Feline mucopolysaccharidosis type VI - characterization of recombinant N-acetylgalactosamine 4-sulfatase and identification of a mutation causing the disease |
Author: | Yogalingam, G. Litjens, T. Bielicki, J. Crawley, A. Muller, V. Anson, D. Hopwood, J. |
Citation: | Journal of Biological Chemistry, 1996; 271(44):27259-27265 |
Publisher: | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
Issue Date: | 1996 |
ISSN: | 0021-9258 1083-351X |
Abstract: | Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive disease caused by a deficiency of N-acetylgalactosamine 4-sulfatase (4S) leading to the lysosomal accumulation and urinary excretion of dermatan sulfate. MPS VI has also been described in the Siamese cat. As an initial step toward enzyme replacement therapy with recombinant feline 4S (rf4S) in MPS VI cats, the feline 4S cDNA was isolated and expressed in CHO-KI cells and rf4S was immunopurified from the culture medium. SDS-polyacrylamide gel electrophoresis analysis showed that the precursor form of immunopurified rf4S was a 66-kDa polypeptide that underwent maturation to a 43-44-kDa polypeptide. Endocytosis of rf4S by cultured feline MPS VI myoblasts was predominantly mediated by a mannose 6-phosphate receptor and resulted in the correction of dermatan sulfate storage. The mutation causing feline MPS VI was identified as a base substitution at codon 476, altering a leucine codon to a proline (L476P). The L476P allele displayed no detectable 4S activity when expressed in CHO-KI cells and was observed only as a "precursor" polypeptide that was not secreted into the medium. Identification of the mutation has allowed the development of a rapid PCR-based screening method to genotype individuals within the cat colony. |
Keywords: | Cells, Cultured CHO Cells Lysosomes Animals Cats Mucopolysaccharidosis VI Cat Diseases Sulfatases N-Acetylgalactosamine-4-Sulfatase Receptor, IGF Type 2 Recombinant Proteins DNA Primers Cloning, Molecular Transfection Polymerase Chain Reaction Base Sequence Kinetics Point Mutation Molecular Sequence Data Cricetinae Genetic Carrier Screening |
DOI: | 10.1074/jbc.271.44.27259 |
Published version: | http://dx.doi.org/10.1074/jbc.271.44.27259 |
Appears in Collections: | Aurora harvest Paediatrics publications |
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