Faculty Research 1990 - 1999


Reversal of pathology in murine mucopolysaccharidosis type VII by somatic cell gene transfer.

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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

JAX Source

Nature 1992 Dec 24-31;360(6406):749-53


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.

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