Faculty Research 1980 - 1989

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

Document Type

Article

Publication Date

1989

Keywords

Animal, Chromosome-Mapping, Disease-Models-Animal, Female, Genes-Recessive, Glucuronidase: ge, df, Liver: ul, Male, Mice, Mice-Inbred-C57BL, Mice-Mutant-Strains: ge, Mucopolysaccharidosis: en, ge, pa, RNA-Messenger: ip, Spleen: ul, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-NON-P-H-S, SUPPORT-U-S-GOVT-P-H-S

First Page

1258

Last Page

1266

JAX Location

1807

JAX Source

J Clin Invest 1989 Apr; 83(4):1258-66.

Grant

AM14770, DK34384

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. J Clin Invest 1989 Apr; 83(4):1258-66.

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