B6.C3-Gusb^mps-2J/BrkJ

Stock number: 006557
Research areas: Developmental Biology Research, Metabolism Research, Mouse/Human Gene Homologs

Description

Mice carrying this spontaneous re-mutation of the Gus gene exhibit a phenotype similar to the Gus^mps mutation, while differences may be attributable to strain background. These mice are useful in studies of human lysosomal storage disease.

Detailed description

Mice homozygous for the Gus^mps-2J allele exhibit a phenotype similar to Gus^mps homozygotes including skeletal deformities, lysosomal storage disease and elevated levels of the lysosomal enzymes alpha-galactosidase and beta-hexosaminidase (Gwynn et al., 1998). Like the Gus^mps heterozygote, Gus^mps-2J heterozygotes have a 26-85% reduction in beta-glucuronidase activity depending on tissue type (Gwynn et al., 1998, Birkenmeier et al., 1989). Homozygotes of both alleles have beta-glucuronidase activity levels at 1% of the control level. Unlike the Gus^mps homozygote, Gus^mps-2J homozygotes on the C3H background live longer, are fertile and can raise litters to weaning age (Gwynn et al., 1998). In addition to a difference in the nature of the mutations between these two alleles, it is also likely that the phenotypic differences are the result of strain background. C3H/HeOuJ mice carry a different set of alleles at the Gus complex than C57BL/6J mice. Beta-glucuronidase activity in C3H/HeOuJ mice is 10-38% that of C57BL/6J mice (Gwynn et al., 1998). The Gus complex alleles determine the rate of enzyme synthesis and may modulate the expression of the beta-glucuronidase deficiency. This strain is a model for the human lysosomal storage disease, mucopolysaccharidosis type VII.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described.

Development

The Gus^mps-2J mutation arose spontaneously in the C3H/HeOuJ (Stock No. 000651) production colony at The Jackson Laboratory (Gwynn et al., 1998). The founder male was identified by a blunter face and shorter, thickened limbs and tail. The mutation was backcrossed to C57BL/6J for 10 generations in the laboratory of staff scientist Dr. Jane Barker. This strain was donated to the Repository in 2006.

Allele

Symbol: Gusb^mps-2J
Name: beta glucuronidase, mucopolysaccharidosis VII 2 Jackson
MGI accession ID: MGI:2152564
Generation method: Spontaneous
Marker symbol: Gusb
Marker name: glucuronidase, beta
Chromosome: 5
Strain of origin: C3H/HeOuJ
Molecular note: Southern blot analysis showed that this allele is the result of a 5.4kb intracisternal A particle (IAP) transposon insertion near the 3' end of intron 8. Homozygous mice have less than 1% of the normal levels of beta glucuronidase activity.