These mice carry a targeted mutation of the Gusb gene and exhibit growth retardation, shortened extremities, and facial dysmorphism.
William S Sly, Saint Louis University Medical Center
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Humanized sequence) | Gusb | glucuronidase, beta |
Homozygous mice are viable but have reduced neonatal survival. Homozygotes are infertile, but fertility can be restored with enzyme replacement therapy. No residual enzyme activity is observed. Homozygous mice are indistinguishable from heterozygous and wild type mice at birth, but show distinct growth retardation, shortened extremities, and facial dysmorphism observable at wean and increasing in severity with age. Long bones of the lower extremities are shortened, broad, and sclerotic. Compared to wild-type, this model has increased urinary glycosaminoglycan and secondary elevation of other lysosomal storage enzymes. Further, homozygous mice show abundant lysosomal storage in liver, kidney, leptomeningeal cells, cornea, spleen, neurons, and retinal pigment epithelium. The phenotype exhibited by this mutant mouse strain is more severe than that observed in a similarly constructed mutant (Stock No. 005644) which bears a L175F point mutation. This strain represents a model of human GUS deficiency characterized by the human E540A mutation that may be useful in studies of severe Mucopolysaccharidosis type VII (MPS VII or Sly Syndrome).
A targeting vector containing exons 1-10 (12.4 kb) of the targeted gene, a loxP-flanked neomycin resistance gene between exons 9 and 10, and herpes simplex virus thymidine kinase gene for selection of properly transfected cells was used in the creation of this mutant. A mutagenic primer was used to introduce a glutamic acid to alanine substitution at residue 536 (E536A) in exon 10 of the targeting vector. The construct was electroporated into the 129X1/SvJ-derived embryonic stem (ES) cell line RW-4. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were backcrossed for germ-line transmission to C57BL/6J females. Offspring were mated with Cre-expressing C57BL/6J to remove the neomycin resistance gene. The neo-excised heterozygotes were backcrossed to C57BL/6J for ten generations.
Allele Name | targeted mutation 1, William S Sly |
---|---|
Allele Type | Targeted (Humanized sequence) |
Allele Synonym(s) | Gustm(E536A)Sly |
Gene Symbol and Name | Gusb, glucuronidase, beta |
Gene Synonym(s) | |
Promoter | Gusb, glucuronidase, beta, mouse, laboratory |
Strain of Origin | 129X1/SvJ |
Chromosome | 5 |
Molecular Note | Site directed mutagenesis was used to introduce a glutamic acid to alanine substitution at residue 536 (E536A) of exon 10. This mutation corresponds to E540A, an active-site nucleophile replacement mutation found in human GUS deficiency. |
Mutations Made By | William Sly, Saint Louis University Medical Center |
When maintaining a live colony, heterozygotes are intercrossed to produce homozygotes, heterozygotes, and wild type mice. Homozygous mice are infertile. Intravenous injection of beta-glucuronidase into young homozygous males will restore fertility (see Sands et al, 1994 J Clin Inv 93:2324-2331).
When using the Gustm(E536A)Sly mouse strain in a publication, please cite the originating article(s) and include JAX stock #005643 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wild-type for Gusb<tm1Sly> |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.