Murine mucopolysaccharidosis type VII. Characterization of a mouse with beta-glucuronidase deficiency.
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.
Birkenmeier
E H
EH
Jackson Laboratory, Bar Harbor, Maine 04609.
Davisson
M T
MT
Beamer
W G
WG
Ganschow
R E
RE
Vogler
C A
CA
Gwynn
B
B
Lyford
K A
KA
Maltais
L M
LM
Wawrzyniak
C J
CJ
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
D012333:RNA, Messenger; D005966:Glucuronidase