Murine mucopolysaccharidosis type VII. Characterization of a mouse with beta-glucuronidase deficiency

J Clin Invest. 1989 Apr;83(4):1258-66. doi: 10.1172/JCI114010.


We have characterized a new mutant mouse that has virtually no beta-glucuronidase activity. This biochemical defect causes a murine lysosomal storage disease that has many interesting similarities to human mucopolysaccharidosis type VII (MPS VII; Sly syndrome; beta-glucuronidase deficiency). Genetic analysis showed that the mutation is inherited as an autosomal recessive that maps to the beta-glucuronidase gene complex, [Gus], on the distal end of chromosome 5. Although there is a greater than 200-fold reduction in the beta-glucuronidase mRNA concentration in mutant tissues, Southern blot analysis failed to detect any abnormalities in the structural gene, Gus-sb, or in 17 kb of 5' flanking and 4 kb of 3' flanking sequences. Surprisingly, a sensitive S1 nuclease assay indicated that the relative level of kidney gusmps mRNA responded normally to androgen induction by increasing approximately 11-fold. Analysis of this mutant mouse may offer valuable information on the pathogenesis of human MPS VII and provide a useful system in which to study bone marrow transplantation and gene transfer methods of therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Chromosome Mapping
  • Disease Models, Animal*
  • Female
  • Genes, Recessive
  • Glucuronidase / deficiency*
  • Glucuronidase / genetics
  • Liver / ultrastructure
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains / genetics*
  • Mucopolysaccharidoses / enzymology
  • Mucopolysaccharidoses / genetics*
  • Mucopolysaccharidoses / pathology
  • RNA, Messenger / isolation & purification
  • Spleen / ultrastructure


  • RNA, Messenger
  • Glucuronidase