Overview

In this B7-DC KO strain, an enhanced green fluorescent protein (EGFP) replaces exon 2, including the initiation codon, of the programmed cell death 1 ligand 2 gene (Pdcd1lg2) - abolishing endogenous gene function. These mice may be useful for studying self tolerance, Th1 and Th2 immune responses.

Donating Investigator

Drew Pardoll, Johns Hopkins University School of Medic

Genetic overview

Genetic Background	Generation

Pdcd1lg2^tm2Dmp

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

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Research Applications

Cancer Research
Immunology, Inflammation and Autoimmunity Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

In this strain, an enhanced green fluorescent protein (EGFP) and a loxP-flanked neomycin resistance (neo) cassette replace exon 2, including the initiation codon, of the programmed cell death 1 ligand 2 (Pdcd1lg2) gene, abolishing gene function. Homozygotes are viable and fertile. The Pdcd1lg2 gene encodes the costimulatory molecule B7-DC which is expressed in dendritic cells (DCs). B7-DC binds to the PD-1 immunoreceptor tyrosine-based inhibitory motif-containing receptor expressed on activated T cells where it regulates self tolerance and immune responses to microbes. These mice exhibit a reduction of intrahepatic tumor-specific CD8 T cells, interferon-γ (IFN-γ) production by CD4 T cells, IFN-γ-dependent humoral responses , antigen-specific CD8 T cell responses, and cytotoxic T lymphocyte (CTL) activity. In these mice hepatic tumors grow more quickly than in wildtype mice. GFP expression is not visible in B7-DC tissue, but the donating investigator reports that GFP expression can be observed in cultured DCs and macrophages when treated with interleukin (IL)-4 or IL-13. These mice may be useful for studying self tolerance, Th1 and Th2 immune responses.

The donating investigator reports that there is no difference in EGFP expression between mice with and without neo.

Development

A targeting vector was designed to replace exon 2, including the initiation codon, of the programmed cell death 1 ligand 2 (Pdcd1lg2) gene with an enhanced green fluorescent protein (EGFP) and a loxP-flanked neomycin resistance (neo) cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells, and chimeras were made by ES cell aggregation. The donating investigator reported that chimeric mice were bred to CMV-Cre mice on a BALB/c background - with the intention of removing the neo cassette (genotyping later determined it retained the neo cassette). The B7-DC KO colony was backcrossed at least nine generations to BALB/c mice (and the CMV-Cre was removed). Following this, the donating investigator reported they mice were backcrossed for at least 12 generations to C57BL/6NCrl (see SNP note below), and then sent to The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony. Genotyping performed at The Jackson Laboratory determined the B7-DC KO allele retained the neo cassette from the original construct.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While 1 of the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Suggestions

Approximate Controls

005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Shin T; Yoshimura K; Shin T; Crafton EB; Tsuchiya H; Housseau F; Koseki H; Schulick RD; Chen L; Pardoll DM. 2005. In vivo costimulatory role of B7-DC in tuning T helper cell 1 and cytotoxic T lymphocyte responses. J Exp Med 201(10):1531-41PubMed: 15897272 MGI: J:99212

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Genetics

Pdcd1lg2^tm2Dmp

Allele Symbol: Pdcd1lg2^tm2Dmp

Allele Name	targeted mutation 2, Drew M Pardoll
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Pdcd1lg2, programmed cell death 1 ligand 2
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	19
Molecular Note	The signal peptide containing the ATG initiation codon was replaced with EGFP and a NEO cassette. This allele was subsequently used to generate Pdcd1lg2^tm1Dmp.
Mutations Made By	Drew Pardoll, Johns Hopkins University School of Medic

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cancer Research
- Increased Tumor Incidence
  - Hepatomas
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
- T Cell Receptor Signaling Defects
- Autoimmunity
Research Tools
- Genetics Research
  - Tissue/Cell Markers

Mammalian Phenotype Terms by Genotype

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

Genotype: Pdcd1lg2^tm1Dmp/Pdcd1lg2^tm1Dmp
C.129-Pdcd1lg2

cellular phenotype

decreased T cell proliferation
- expansion of adoptively transferred naive D011.10 CD4 T cells is reduced in the spleen (by 34%), peripheral lymph nodes (50%), hepatic lymph nodes (42%), and liver (61%)
- however; overall cell numbers and proportions of T, B, natural killer, natural killer T, and dendritic cells in the thymus and spleen and cell yield from bone marrow-derived dendritic cell cultures are similar to wild-type
- under Th1-generating conditions T cells cultured with mutant bone marrow-derived dendritic cells produce 40% fewer IFNG+ cells; however no difference in proliferation was seen under Th2-generating conditions

mortality/aging

increased sensitivity to induced morbidity/mortality
- homozygotes bearing injected with CT26 colon tumor cells die sooner compared to wild-type mice

neoplasm

increased tumor growth/size
- CT26 tumor cell-derived hepatic tumors grow more rapidly

hematopoietic system phenotype

abnormal cytotoxic T cell physiology
- cytotoxic T cell activity is reduced by about 50% in homozygous mice immunized with hemagglutinin-specific CD8 T cells then injected with BALB/c splenocytes loaded with hemagglutinin compared to wild-type mice treated in the same way

decreased IgG2a level
- homozygous null mice immunized with a T cell dependent antigen produced significantly less IgG2a

decreased T cell proliferation
- expansion of adoptively transferred naive D011.10 CD4 T cells is reduced in the spleen (by 34%), peripheral lymph nodes (50%), hepatic lymph nodes (42%), and liver (61%)
- however; overall cell numbers and proportions of T, B, natural killer, natural killer T, and dendritic cells in the thymus and spleen and cell yield from bone marrow-derived dendritic cell cultures are similar to wild-type
- under Th1-generating conditions T cells cultured with mutant bone marrow-derived dendritic cells produce 40% fewer IFNG+ cells; however no difference in proliferation was seen under Th2-generating conditions

immune system phenotype

abnormal cytokine secretion
- significantly less IFNG and IL-2 and more IL-4 are produced in homozygotes immunized with peptide-pulsed homozygous bone marrow-derived dendritic cells compared to wild-type mice immunized with peptide pulsed wild-type bone marrow-derived dendritic cells

abnormal cytotoxic T cell physiology
- cytotoxic T cell activity is reduced by about 50% in homozygous mice immunized with hemagglutinin-specific CD8 T cells then injected with BALB/c splenocytes loaded with hemagglutinin compared to wild-type mice treated in the same way

decreased IgG2a level
- homozygous null mice immunized with a T cell dependent antigen produced significantly less IgG2a

decreased T cell proliferation
- expansion of adoptively transferred naive D011.10 CD4 T cells is reduced in the spleen (by 34%), peripheral lymph nodes (50%), hepatic lymph nodes (42%), and liver (61%)
- however; overall cell numbers and proportions of T, B, natural killer, natural killer T, and dendritic cells in the thymus and spleen and cell yield from bone marrow-derived dendritic cell cultures are similar to wild-type
- under Th1-generating conditions T cells cultured with mutant bone marrow-derived dendritic cells produce 40% fewer IFNG+ cells; however no difference in proliferation was seen under Th2-generating conditions

Genotype: Pdcd1lg2^tm2Dmp/Pdcd1lg2⁺
involves: 129S1/Sv * 129X1/SvJ

mammalian phenotype

no phenotypic analysis

References

Shin T; Yoshimura K; Shin T; Crafton EB; Tsuchiya H; Housseau F; Koseki H; Schulick RD; Chen L; Pardoll DM. 2005. In vivo costimulatory role of B7-DC in tuning T helper cell 1 and cytotoxic T lymphocyte responses. J Exp Med 201(10):1531-41PubMed: 15897272 MGI: J:99212

Additional - Pdcd1lg2^tm2Dmp related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Pdcd1lg2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the B6N.129(Cg)-Pdcd1lg2^tm2Dmp/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017515 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 Pdcd1lg2<tm1Dmp>

Related Products and Services

Frozen Mouse Embryo	B6N.129(Cg)-Pdcd1lg2<tm2Dmp>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6N.129(Cg)-Pdcd1lg2<tm2Dmp>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6N.129(Cg)-Pdcd1lg2<tm2Dmp>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6N.129(Cg)-Pdcd1lg2<tm2Dmp>/J Frozen Embryo	$3373.50

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Pdcd1lg2tm2Dmp

Allele Symbol: Pdcd1lg2tm2Dmp

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Pdcd1lg2tm1Dmp/Pdcd1lg2tm1DmpC.129-Pdcd1lg2

cellular phenotype

mortality/aging

neoplasm

hematopoietic system phenotype

immune system phenotype

Genotype: Pdcd1lg2tm2Dmp/Pdcd1lg2+involves: 129S1/Sv * 129X1/SvJ

mammalian phenotype

References

Additional - Pdcd1lg2tm2Dmp 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

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Pdcd1lg2^tm2Dmp

Allele Symbol: Pdcd1lg2^tm2Dmp

Genotype: Pdcd1lg2^tm1Dmp/Pdcd1lg2^tm1Dmp
C.129-Pdcd1lg2

Genotype: Pdcd1lg2^tm2Dmp/Pdcd1lg2⁺
involves: 129S1/Sv * 129X1/SvJ

Additional - Pdcd1lg2^tm2Dmp related