Murine Mucopolysaccharidosis Type

We have characterized a new mutant mouse that has virtually no /-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; fl-glucuronidase deficiency). Genetic analysis showed that the mutation is inherited as an autosomal recessive that maps to the fl-glucuronidase gene complex, [Gus], on the distal end of chromosome 5. Although there is a > 200fold reduction in the fl-glucuronidase mRNA concentration in mutant tissues, Southern blot analysis failed to detect any abnormalities in the structural gene, Gus-s", 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 gus"P' mRNA responded normally to androgen induction by increasing 1-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.