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Type: Journal article
Title: Regulation of N-acetylgalactosamine 4-sulfatase expression in retrovirus-transduced feline mucopolysaccharidosis type VI muscle cells
Author: Yogalingam, G.
Muller, V.
Hopwood, J.
Anson, D.
Citation: DNA and Cell Biology, 1999; 18(3):187-195
Issue Date: 1999
ISSN: 1044-5498
Statement of
Gouri Yogalingam, Vivienne Muller, John J. Hopwood, Donald S. Anson
Abstract: As a preliminary step toward muscle-mediated gene therapy in the mucopolysaccharidosis (MPS) type VI cat, we have analyzed the transcriptional regulation of feline N-acetylgalactosamine 4-sulfatase (f4S) gene expression from various retroviral constructs in primary cultures of muscle cells. Two retroviral constructs were made containing the f4S cDNA under the transcriptional control of the human polypeptide chain-elongation factor 1alpha (EF1alpha) gene promoter or the cytomegalovirus (CMV) immediate-early promoter. Two further retroviral constructs were made with the murine muscle creatine kinase (mck) enhancer sequence upstream of the internal promoter. Virus made from each construct was used to transduce feline MPS VI myoblasts. The mck enhancer significantly upregulated f4S gene expression from both the EF1alpha promoter and the CMV promoter in transduced myoblasts and in differentiated myofibers. The highest level of 4S activity was observed in myoblasts and myofibers transduced with the retroviral construct Lmckcmv4S, in which the f4S gene is under the transcriptional regulation of the mck enhancer and CMV immediate-early promoter. Lmckcmv4S-transduced myofibers demonstrated correction of glycosaminoglycan storage and contained a 58-fold elevated level of 4S activity compared with normal myofibers. Recombinant f4S secreted from Lmckcmv4S-transduced myofibers was endocytosed by feline MPS VI myofibers, leading to correction of the biochemical storage phenotype.
Keywords: Muscle, Skeletal
Cells, Cultured
Cell Line
Mucopolysaccharidosis VI
Growth Hormone
Peptide Elongation Factor 1
Creatine Kinase
Recombinant Fusion Proteins
Peptide Elongation Factors
Poly A
Cloning, Molecular
Gene Transfer Techniques
Cell Differentiation
Gene Expression Regulation, Enzymologic
Enhancer Elements, Genetic
Promoter Regions, Genetic
Muscle Fibers, Skeletal
DOI: 10.1089/104454999315402
Appears in Collections:Aurora harvest
Paediatrics publications

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