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. 1989 Apr;83(4):1258–1266. doi: 10.1172/JCI114010

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

E H Birkenmeier 1, M T Davisson 1, W G Beamer 1, R E Ganschow 1, C A Vogler 1, B Gwynn 1, K A Lyford 1, L M Maltais 1, C J Wawrzyniak 1
PMCID: PMC303816  PMID: 2495302

Abstract

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.

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