Overview

These targeted mutant mice possess insertions in the IgV exons of Pdcd1lg2 (programmed cell death 1 ligand 2) and Cd274, which affects lymphocyte activation and may be useful in studies of T cell regulation, activation and tolerance.

Donating Investigator

Arlene H Sharpe, Harvard Medical School

Genetic overview

Genetic Background	Generation

Cd274^tm2Shr

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Cd274	CD274 antigen

Pdcd1lg2^tm4Shr

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Pdcd1lg2	programmed cell death 1 ligand 2

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research

View All Research Applications

Details

Detailed Description

Mice that are homozygous for both targeted alleles are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Mice exhibit defects in lymphocyte activation. This mutant mouse strain may be useful in studies of T cell regulation, activation and tolerance.

Development

The Cd274^tm2Shr targeting vector was used to re-target Pdcd1lg2 by replacing the IgV exon of with a hygromycin resistance cassette. The original Cd274^tm2Shr targeting vector contains neomycin resistance and herpes simplex virus thymidine kinase genes that disrupt the signal exon and two-thirds of the IgV exon. The construct was electroporated into heterozygous Cd274^tm2Shr 129S4/SvJae J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to 129S4/SvJae mice.

Control Suggestions

009104 129S4/SvJaeJ

Additional Information

Considerations for Choosing Controls

Selected References

Sharpe A. 2010. Generation of PD-L1/PD-L2 mutant MGI Direct Data SubmissionMGI: J:160970

View All References

Genetics

Cd274^tm2Shr

Allele Symbol: Cd274^tm2Shr

Allele Name	targeted mutation 2, Arlene H Sharpe
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	PD-L1^-
Gene Symbol and Name	Cd274, CD274 antigen
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	19
Molecular Note	A neomycin resistance gene replaced the signal exon and two-thirds of the IgV exon. Southern blot confirmed recombination.
Mutations Made By	Arlene Sharpe, Harvard Medical School

Pdcd1lg2^tm4Shr

Allele Symbol: Pdcd1lg2^tm4Shr

Allele Name	targeted mutation 4, Arlene H Sharpe
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	PDL1/L2
Gene Symbol and Name	Pdcd1lg2, programmed cell death 1 ligand 2
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	19
Molecular Note	A targeting vector was designed to replace the the IgV exon with a hygromycin resistance gene in ES cells containing the Cd274^tm2Shr allele in which the CD274 antigen signal and two-thirds of the IgV exon were replaced with a neomycin cassette.
Mutations Made By	Arlene Sharpe, Harvard Medical School

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - T cell deficiency

Mammalian Phenotype Terms by Genotype

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

Genotype: Cd274^tm2Shr/Cd274^tm2Shr Pdcd1lg2^tm4Shr/Pdcd1lg2^tm4Shr
involves: 129S4/SvJae

immune system phenotype

abnormal immune system physiology
- mice are reported to exhibit a defect in T celll tolerance and increased immune activation

References

Sharpe A. 2010. Generation of PD-L1/PD-L2 mutant MGI Direct Data SubmissionMGI: J:160970

Additional - Cd274^tm2Shr related

Additional - Pdcd1lg2^tm4Shr related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Pdcd1lg2alternate1
- Separated PCR:Cd274
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice may be bred as homozygous for both targeted alleles.
- Additional Breeding and Husbandry Support
Citation
When using the 129S4/SvJae-Cd274^tm2Shr Pdcd1lg2^tm4Shr/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32239 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

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

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Cd274tm2Shr

Allele Symbol: Cd274tm2Shr

Pdcd1lg2tm4Shr

Allele Symbol: Pdcd1lg2tm4Shr

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Cd274tm2Shr/Cd274tm2Shr Pdcd1lg2tm4Shr/Pdcd1lg2tm4Shrinvolves: 129S4/SvJae

immune system phenotype

References

Additional - Cd274tm2Shr related

Additional - Pdcd1lg2tm4Shr related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Cd274^tm2Shr

Allele Symbol: Cd274^tm2Shr

Pdcd1lg2^tm4Shr

Allele Symbol: Pdcd1lg2^tm4Shr

Genotype: Cd274^tm2Shr/Cd274^tm2Shr Pdcd1lg2^tm4Shr/Pdcd1lg2^tm4Shr
involves: 129S4/SvJae

Additional - Cd274^tm2Shr related

Additional - Pdcd1lg2^tm4Shr related