Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/7200
Citations | ||
Scopus | Web of ScienceĀ® | Altmetric |
---|---|---|
?
|
?
|
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 |
Publisher: | MARY ANN LIEBERT INC PUBL |
Issue Date: | 1999 |
ISSN: | 1044-5498 1557-7430 |
Statement of Responsibility: | 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 Animals Cats Humans Mice Cytomegalovirus Retroviridae Mucopolysaccharidosis VI Growth Hormone Peptide Elongation Factor 1 N-Acetylgalactosamine-4-Sulfatase Creatine Kinase Glycosaminoglycans Recombinant Fusion Proteins Peptide Elongation Factors Poly A Cloning, Molecular Gene Transfer Techniques Transfection Cell Differentiation Gene Expression Regulation, Enzymologic Enhancer Elements, Genetic Promoter Regions, Genetic Muscle Fibers, Skeletal |
DOI: | 10.1089/104454999315402 |
Published version: | http://dx.doi.org/10.1089/104454999315402 |
Appears in Collections: | Aurora harvest Paediatrics publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.