Faculty Research 1990 - 1999


A single-base-pair deletion in the beta-glucuronidase gene accounts for the phenotype of murine mucopolysaccharidosis type VII.

Document Type


Publication Date



Amino-Acid-Sequence, Animal, Base-Sequence, Cloning-Molecular, Exons: ge, Frameshift-Mutation: ge, Genome, Glucuronidase: ge, Mice, Mice-Mutant-Strains, Molecular-Sequence-Data, Mucopolysaccharidosis-VII: en, ge, ve, Mutagenesis-Site-Directed, Phenotype, Restriction-Fragment-Length-Polymorphisms, Restriction-Mapping, Rodent-Diseases: ge, Sequence-Analysis-DNA, Sequence-Deletion, Sequence-Homology-Amino-Acid, Sequence-Homology-Nucleic-Acid, SUPPORT-U-S-GOVT-P-H-S, Transfection

JAX Source

Proc Natl Acad Sci U S A 1993 Jul 15;90(14):6567-71




Murine mucopolysaccharidosis type VII is a heritable disease caused by a spontaneous mutation, gus(mps), closely linked to the beta-glucuronidase structural gene on chromosome 5. Mice homozygous for the mutation have a > 200-fold decrease in beta-glucuronidase mRNA levels and virtually no enzyme activity detectable by a sensitive fluorometric assay. Approximately 20 kb of genomic DNA containing the beta-glucuronidase gene Gus and > 2 kb of 5' and 3' flanking sequences were cloned from both a gus(mps)/gus(mps) mouse and a +/+ mouse of the progenitor strain. Restriction enzyme digests containing DNA fragments 20-400 bp in length were generated from each of the two Gus alleles and then compared by using nondenaturing polyacrylamide DNA-sequencing gels. This method rapidly identified a large number of restriction sites and was sensitive enough to detect a restriction fragment length variation resulting from a 1-bp deletion in the gus(mps) allele. DNA-sequence analysis of the mutant genomic fragment showed that the 1-bp deletion created a frameshift mutation within exon 10. Insertion of the deleted nucleotide by oligonucleotide site-directed mutagenesis restored function to the corrected mutant gene when transfected into gus(mps)/gus(mps) fibroblasts. We concluded that the frameshift mutation, which introduces a premature stop codon at codon 497 in exon 10, accounts for the molecular, biochemical, and pathological abnormalities associated with the gus(mps) phenotype.

Please contact the Joan Staats Library for information regarding this document.