title: Murine mucopolysaccharidosis type VII. Characterization of a mouse with beta-glucuronidase deficiency.
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.
authors.affiliation: Jackson Laboratory, Bar Harbor, Maine 04609.
authors.forename: E H
authors.initials: EH
authors.lastname: Birkenmeier
authors.forename: M T
authors.initials: MT
authors.lastname: Davisson
authors.forename: W G
authors.initials: WG
authors.lastname: Beamer
authors.forename: R E
authors.initials: RE
authors.lastname: Ganschow
authors.forename: C A
authors.initials: CA
authors.lastname: Vogler
authors.forename: B
authors.initials: B
authors.lastname: Gwynn
authors.forename: K A
authors.initials: KA
authors.lastname: Lyford
authors.forename: L M
authors.initials: LM
authors.lastname: Maltais
authors.forename: C J
authors.initials: CJ
authors.lastname: Wawrzyniak
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D005260:Female; D005808:Genes, Recessive; D005966:Glucuronidase / Q000172:deficiency* / Q000235:genetics; D008099:Liver / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000235:genetics*; D009083:Mucopolysaccharidoses / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000302:isolation & purification; D013154:Spleen / Q000648:ultrastructure
chemical_list: D012333:RNA, Messenger; D005966:Glucuronidase