Overview

These mice carry a floxed/reversible gene trap allele of the mouse Prg4 gene designed to produce membrane-anchored β-galactosidase instead of lubricin in cells where Prg4 is normally expressed. Cre-mediated excision of the genetrap restores lubricin expression.

Donating Investigator

Matthew Warman, Boston Children's Hospital, Harvard Medical School

Genetic overview

Genetic Background	Generation

Prg4^tm2Mawa

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Reporter, Null/Knockout, Inserted expressed sequence, Transactivator)	Prg4	proteoglycan 4 (megakaryocyte stimulating factor, articular superficial zone protein)

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Research Applications

Research Tools
Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Congenital deficiency of the principal boundary lubricant in cartilage (lubricin, encoded by the gene Prg4, proteoglycan 4 (megakaryocyte stimulating factor, articular superficial zone protein)) increases joint friction and causes progressive joint failure.

These mice carry a floxed gene trap allele of the mouse Prg4 gene designed to produce membrane-anchored β-galactosidase instead of lubricin in cells where Prg4 is normally expressed. The genetrap allele does not express wildtype Prg4 mRNA, as determined by RT-PCR. Phenotypic features of the genetrap allele recapitulate those of Prg4 knockout alleles (protein deposition on cartilage by 2 months of age, increased articular joint friction, etc. - see Stock No. 025737).

Cre-mediated excision of the genetrap restores lubricin expression and the wildtype condition. Scattered areas of β-galactosidase expression may still be present in the synovium of treated mice, however, suggesting that lubricin expression may not be restored in every type B synoviocyte.

Restoring gene function prior to conception through crosses with germline-specific EIIa-cre (see Stock No. 003724) prevents cartilage damage. Tamoxifen-induced restoration of gene function (through crosses with Gt(ROSA)26Sor^CreERt2 (see Stock No. 008463)) at 3-weeks-of-age improves, but does not normalize, joint histology or whole joint friction. Restoring gene function in 2-month-old or 6-month-old mice has no beneficial effect.

The gene trap design additionally includes a reverse tet transactivator (rtTA) cassette.

Development

A targeting vector was designed to contain a loxP-flanked artificial exon that contains a strong splice acceptor, an in-frame lacZ coding sequence, an internal ribosome entry site (IRES), a reverse tet transactivator (rtTA) cassette, and a neomycin selection cassette driven by its own promoter. The mutation was introduced to intron 2 of the Prg4 gene via homologous recombination in (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. The donating laboratory maintained this strain on a mixed C57BL/6J-129 genetic background.

Expression Data

Expressed Gene	Bgeo, fusion of beta-galactosidase and neomycin phosphotransferase genes, E. coli
Expressed Gene	rtTA, reverse tetracycline-controlled transactivator, E. coli
Site of Expression	ß-galactosidase instead of lubricin is expressed in cartilage.

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Genetics

Prg4^tm2Mawa

Allele Symbol: Prg4^tm2Mawa

Allele Name	targeted mutation 2, Matthew Warman
Allele Type	Targeted (Conditional ready (e.g. floxed), Reporter, Null/Knockout, Inserted expressed sequence, Transactivator)
Allele Synonym(s)	Prg4:GT; Prg4^GT
Gene Symbol and Name	Prg4, proteoglycan 4 (megakaryocyte stimulating factor, articular superficial zone protein)
Gene Synonym(s)
Expressed Gene	Bgeo, fusion of beta-galactosidase and neomycin phosphotransferase genes, E. coli
Expressed Gene	rtTA, reverse tetracycline-controlled transactivator, E. coli
Site of Expression	ß-galactosidase instead of lubricin is expressed in cartilage.
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	1
Molecular Note	A targeting vector containing a loxP-flanked artifical exon that contains a strong splice acceptor, an in-frame Bgeo lacZ coding sequence, an internal ribosome entry site (IRES), a reverse tet transactivator (rtTA) cassette with a polyA signal, and a neomycin selection cassette driven by its own promoter was inserted into intron 2 of the gene. The allele does not express wild-type Prg4 mRNA, as determined by RT-PCR. Cre-mediated excision of the targeting vector leaves one loxP in intron 2 and allows expression of Prg4 mRNA.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Immunology, Inflammation and Autoimmunity Research
- Developmental Biology Research
  - Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences
- lacZ Expression
- Internal/Organ Research
Immunology, Inflammation and Autoimmunity Research
- Inflammation
  - rheumatoid arthritis

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Prg4^tm2Mawa/Prg4^tm2Mawa
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

skeleton phenotype

abnormal skeleton morphology
- phenotype is stated to be identical to that of Prg4^tm1Mawa homozygotes

References

Additional - Prg4^tm2Mawa related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Prg4alternate1
- Standard PCR:Generic Neo
- Standard PCR:Generic LacZ Melt Curve Analysis
- Probe:Generic Neo
- Probe:Generic LacZ Probe
- Genotyping resources and troubleshooting
Breeding Considerations

Homozygotes and heterozygotes are viable and fertile.
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Citation
When using the B6;129-Prg4^tm2Mawa/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025740 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 for Prg4<tm2Mawa>

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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General Terms and Conditions

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Prg4tm2Mawa

Allele Symbol: Prg4tm2Mawa

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Prg4tm2Mawa/Prg4tm2Mawainvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

skeleton phenotype

References

Additional - Prg4tm2Mawa related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

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

Prg4^tm2Mawa

Allele Symbol: Prg4^tm2Mawa

Genotype: Prg4^tm2Mawa/Prg4^tm2Mawa
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Additional - Prg4^tm2Mawa related