Overview

Homozygous mice for this targeted mutation in beta glucuronidase (Gusb) exhibit growth retardation, shortened extremities, and facial dysmorphism. This model has increased urinary glycosaminoglycan and secondary elevation of other lysosomal storage enzymes. This strain represents a model of human GUS deficiency characterized by the most prevalent human mutation, L176F, and is associated with mild Mucopolysaccharidosis type VII (MPS VII or Sly Syndrome).

Donating Investigator

William S Sly, Saint Louis University Medical Center

Genetic overview

Genetic Background	Generation

Gusb^tm3Sly

Allele Type	Gene Symbol	Gene Name
Targeted (Humanized sequence)	Gusb	glucuronidase, beta

View Genetics

Research Applications

Developmental Biology Research
Metabolism Research
Internal/Organ Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

Homozygous mice are viable but infertile. Fertility can be restored with enzyme replacement therapy. Less than 1% residual enzyme activity is observed. Homozygous mice are indistinguishable from wild type mice at birth, but show distinct growth retardation, shortened extremities, and facial dysmorphism observable at three months with a moderate increase 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, and retinal pigment epithelium. The phenotype exhibited by this mutant mouse strain is less severe than that observed in a similarly constructed mutant (Stock No. 005643) which bears a E536A point mutation. This strain represents a model of human GUS deficiency characterized by the most prevalent human mutation, L176F, and is associated with mild 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 leucine to phenylalanine substitution at residue 175 (L175F) in exon 2 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 Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):14982-7PubMed: 12403825 MGI: J:81792

View All References

Genetics

Gusb^tm3Sly

Allele Symbol: Gusb^tm3Sly

Allele Name	targeted mutation 3, William S Sly
Allele Type	Targeted (Humanized sequence)
Allele Synonym(s)	Gus^tm(L175F)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 leucine to phenylalanine subsitution at residue 175 (L175F) of exon 2. This mutation corresponds to L176F, the most common mutation found in human GUS deficiency.
Mutations Made By	William Sly, Saint Louis University Medical Center

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Sly syndrome

Research Areas By Phenotype

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

Developmental Biology Research
- Growth Defects
  - Growth Defects (homozygous)
- Skeletal Defects
Metabolism Research
- Enzyme Deficiency
Internal/Organ Research
- Liver Defects
- Kidney Defects
  - lysosomal enzyme abnormalities

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Gusb^tm3Sly/Gusb^tm3Sly
involves: 129X1/SvJ * C57BL/6J

cellular phenotype

abnormal lysosome morphology
- lysosomal storage in liver, kidney, leptomeningeal cells, cornea, spleen, neurons, and retinal pigment epithelium, but to a lesser extent than in homozygous Gsub^tm1Sly mice

craniofacial phenotype

abnormal facial morphology
- facial dysmorphism is first observed around 3 months of age and increases slowly with age

growth/size/body region phenotype

abnormal facial morphology
- facial dysmorphism is first observed around 3 months of age and increases slowly with age

homeostasis/metabolism phenotype

increased urine glycosaminoglycan level
- 3-fold increase in glycosaminoglycan levels in urine than in wild-type

renal/urinary system phenotype

increased urine glycosaminoglycan level
- 3-fold increase in glycosaminoglycan levels in urine than in wild-type

skeleton phenotype

abnormal articular cartilage morphology
- articular cartilage is somewhat distorted with chondrocytes

abnormal long bone morphology
- long bones are sclerotic, but to a much lesser extent than in homozygous Gsub^tm1Sly mice

decreased length of long bones
- long bones are shortened but to a much lesser extent than in homozygous Gsub^tm1Sly mice

increased diameter of long bones
- long bones are broad but to a much lesser extent than in homozygous Gsub^tm1Sly mice

References

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):14982-7PubMed: 12403825 MGI: J:81792

Additional - Gusb^tm3Sly related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Pyrosequencing:Gusb
- Genotyping resources and troubleshooting
Breeding Considerations

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).
- Additional Breeding and Husbandry Support
Citation
When using the B6.129X-Gusb^tm3Sly/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #005644 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Gusb<tm3Sly>

Related Products and Services

Frozen Mouse Embryo	B6.129X-Gusb<tm3Sly>/J	$2595.00
Frozen Mouse Embryo	B6.129X-Gusb<tm3Sly>/J	$2595.00
Frozen Mouse Embryo	B6.129X-Gusb<tm3Sly>/J	$3373.50
Frozen Mouse Embryo	B6.129X-Gusb<tm3Sly>/J	$3373.50

Payment Terms and Conditions

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's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Gusbtm3Sly

Allele Symbol: Gusbtm3Sly

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Gusbtm3Sly/Gusbtm3Slyinvolves: 129X1/SvJ * C57BL/6J

cellular phenotype

craniofacial phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

renal/urinary system phenotype

skeleton phenotype

References

Additional - Gusbtm3Sly related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Gusb^tm3Sly

Allele Symbol: Gusb^tm3Sly

Genotype: Gusb^tm3Sly/Gusb^tm3Sly
involves: 129X1/SvJ * C57BL/6J

Additional - Gusb^tm3Sly related