Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

Journal Article · Tue May 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.10.3914· OSTI ID:5463599

Kyle, J W; Vogler, C; Hoffmann, J W; Sly, W S ^[1]; Birkenmeier, E H; Gwynn, B ^[2]

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1. St. Louis Univ. School of Medicine, MO (USA)
2. Jackson Laboratory, Bar Harbor, ME (USA)

The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

• OSTI ID: 5463599
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:10; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GLUCURONIDASE
GENETIC ENGINEERING
POLYSACCHARIDES
HEREDITARY DISEASES
ENZYME ACTIVITY
GENE RECOMBINATION
GENOTYPE
LYSOSOMES
MAN
MICE
TRANSMISSION ELECTRON MICROSCOPY
ANIMALS
BIOTECHNOLOGY
CARBOHYDRATES
DISEASES
ELECTRON MICROSCOPY
ENZYMES
GLYCOSYL HYDROLASES
HYDROLASES
MAMMALS
MICROSCOPY
O-GLYCOSYL HYDROLASES
ORGANIC COMPOUNDS
PRIMATES
RODENTS
SACCHARIDES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques