Faculty Research 1990 - 1999
Reversal of pathology in murine mucopolysaccharidosis type VII by somatic cell gene transfer.
Document Type
Article
Publication Date
1992
Keywords
Bone-Marrow: en, Bone-Marrow-Transplantation, Gene-Therapy, Genetic-Vectors, Glucuronidase: ge, Glycosaminoglycans: me, Hematopoietic-Stem-Cells: en, Liver: en, ul, Lysosomes: me, Mice, Mucopolysaccharidosis-VII: th, Polymerase-Chain-Reaction, Retroviridae: ge, Spleen: en, tr, ul, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Transfection
First Page
749
Last Page
753
JAX Source
Nature 1992 Dec 24-31;360(6406):749-53
Abstract
An inherited deficiency of beta-glucuronidase in humans, mice and dogs causes mucopolysaccharidosis VII (Sly syndrome), a progressive degenerative disease that reduces lifespan (to an average of 5 months in mice) and results from lysosomal storage of undegraded glycosaminoglycans in the spleen, liver, kidney, cornea, brain and skeletal system. Bone marrow transplantation in mutant mice provides a source of normal enzyme ('cross-correction'), which substantially improves the clinical condition and extends the average lifespan to 18 months. Gene therapy by transfer of a beta-glucuronidase gene into mutant haematopoietic stem cells is an alternative approach, but it is not known whether the low expression of vector-transferred genes in vivo would be sufficiently effective. Here we show that retroviral vector-mediated transfer of the gene to mutant stem cells results in long-term expression of low levels of beta-glucuronidase which partially corrects the disease by reducing lysosomal storage in liver and spleen.
Recommended Citation
Wolfe JH,
Sands MS,
Barker JE,
Gwynn B,
Rowe LB,
Vogler CA,
Birkenmeier EH.
Reversal of pathology in murine mucopolysaccharidosis type VII by somatic cell gene transfer. Nature 1992 Dec 24-31;360(6406):749-53