Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.129X-Gusb(tm1Sly)/J    (Changed: 23-NOV-05 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N11p   Donating Investigator William Sly,   Saint Louis University Medical Center

Description
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).

Development
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.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Gusb

006564	B6(C)-KitW-41J Gusbmps/BrkJ
005644	B6.129X-Gusbtm3Sly/J
001603	B6.A-Gusba/J
006559	B6.C-H2-Kbm1/ByBir-Gusbmps/BrkJ
000256	B6.C-H2-Kbm1/ByBir-Gusbmps/J
001598	B6.C3-Gusbh/J
006557	B6.C3-Gusbmps-2J/BrkJ
001599	B6.CAST-Gusbcs/J
006562	B6.CBy(Cg)-Gusbmps Gpi1a-m1J/BrkJ
001604	B6.Cg-Es22h Es1b Gusbh/J
006407	B6.Cg-Gusbmps/BrkJ
002086	B6.Cg-Gusbmps Tg(Gussx)1Wat/J
001605	B6.Cg-Gusbw12/CvJ
001608	B6.Cg-Gusbw26/CvJ
006558	B6.Cg-H2-Kbm1 Tg(GUSB)4Sly/SndsJ
001602	B6.MOR-Gusbw5/CvJ
001597	B6.PAC-Gusbn/J
003525	C3H/HeOuJ-Gusbmps-2J/BrkJ
005322	C57BL/6J-Gusbmps-3J/J
005053	NOD.Cg-Prkdcscid Gusbmps/SndsJ
001880	STOCK Gusbmps Tg(GUSB)4Sly/BirJ

View Strains carrying other alleles of Gusb     (21 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Mucopolysaccharidosis Type VII - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Gusb^tm1Sly/Gusb^tm1Sly

        involves: 129X1/SvJ * C57BL/6J

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:81792)
  • fewer than the expected numbers of homozygotes are observed at weaning
• craniofacial phenotype
• short snout (MGI Ref ID J:81792)
  • by weaning, mutants have shortened faces
• growth/size phenotype
• decreased body size (MGI Ref ID J:81792)
  • slightly smaller at weaning
• postnatal growth retardation (MGI Ref ID J:81792)
  • growth retardation with age
• limbs/digits/tail phenotype
• abnormal skeleton extremities morphology (MGI Ref ID J:81792)
  • extremities become shortened with age
• decreased length of long bones (MGI Ref ID J:81792)
• increased diameter of long bones (MGI Ref ID J:81792)
  • long bones are broad
• short limbs (MGI Ref ID J:81792)
• skeleton phenotype
• abnormal articular cartilage morphology (MGI Ref ID J:81792)
  • articular cartilage is distorted with chondrocytes and stromal cells in the synovium and meniscus, and shows cytoplasmic distention caused by lysosomal storage
• abnormal epiphyseal plate morphology (MGI Ref ID J:81792)
  • growth plate is thickened
  • chondrocytes in the growth plate are haphazardly arranged
• abnormal skeleton extremities morphology (MGI Ref ID J:81792)
  • extremities become shortened with age
• decreased length of long bones (MGI Ref ID J:81792)
• increased diameter of long bones (MGI Ref ID J:81792)
  • long bones are broad
• behavior/neurological phenotype
• abnormal gait (MGI Ref ID J:81792)
  • hobbled gait
• cellular phenotype
• abnormal lysosome morphology (MGI Ref ID J:81792)
  • abundant lysosomal storage in liver, kidney, leptomeningeal cells, cornea, spleen, neurons, and retinal pigment epithelium
• accumulation of giant lysosomes in kidney/renal tubule cells (MGI Ref ID J:81792)
• homeostasis/metabolism phenotype
• abnormal urine homeostasis (MGI Ref ID J:87155)
  • 10-fold increase in glycoaminoglycan levels in urine than in wild-type
• renal/urinary system phenotype
• abnormal urine homeostasis (MGI Ref ID J:87155)
  • 10-fold increase in glycoaminoglycan levels in urine than in wild-type
• accumulation of giant lysosomes in kidney/renal tubule cells (MGI Ref ID J:81792)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Developmental Biology Research
Growth Defects
      Growth Defects (homozygous)
Skeletal Defects

Internal/Organ Research
Kidney Defects
      lysosomal enzyme abnormalities
Liver Defects
Spleen Defects

Metabolism Research
Enzyme Deficiency

Genes & Alleles

Gene & Allele Information

Allele Symbol		Gusbtm1Sly
Allele Name		targeted mutation 1, William S Sly
Allele Type		Targeted (knock-in)
Common Name(s)		Gustm(E536A)Sly;
Mutation Made By		William Sly,   Saint Louis University Medical Center
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Gusb, glucuronidase, beta
Chromosome		5
Gene Common Name(s)		AI747421; Ac2-223; FLJ39445; Gur; Gus; Gus-r; Gus-s; Gus-t; Gus-u; Gut; MPS7; adipose storage deficiency; asd; beta-glucuronidase regulator; beta-glucuronidase structural; beta-glucuronidase systemic regulator; beta-glucuronidase temporal; expressed sequence AI747421; g;
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. [MGI Ref ID J:81792]

Genotyping

Genotyping Information

Genotyping Protocols

Gusb^tm1Sly, Restriction Enzyme Digest

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Tomatsu S; Orii KO; Vogler C; Grubb JH; Snella EM; Gutierrez MA; Dieter T; Sukegawa K; Orii T; Kondo N; Sly WS. 2002. Missense models [Gustm(E536A)Sly, Gustm(E536Q)Sly, and Gustm(L175F)Sly] of murine mucopolysaccharidosis type VII produced by targeted mutagenesis. Proc Natl Acad Sci U S A 99(23):14982-7. [PubMed: 12403825]  [MGI Ref ID J:81792]

Additional References

Gusb^tm1Sly related

Tomatsu S; Orii KO; Vogler C; Nakayama J; Levy B; Grubb JH; Gutierrez MA; Shim S; Yamaguchi S; Nishioka T; Montano AM; Noguchi A; Orii T; Kondo N; Sly WS. 2003. Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease. Hum Mol Genet 12(24):3349-58. [PubMed: 14583446]  [MGI Ref ID J:87155]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	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).

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location). This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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Terms of Use

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Contact information

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