Overview

These Cd27 knockout mice have impaired T cell responses to viruses as well as delayed memory cell responses. They may have applications in studies related to immune cell development and peripheral expansion.

Donating Investigator

Jannie Borst, The Netherlands Cancer Institute

Genetic overview

Genetic Background	Generation

Cd27^tm1Jbo

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Cd27	CD27 antigen

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Research Applications

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

A hygro cassette replaces the entire coding region of the CD27 antigen (Cd27; Tnfrsf7) gene, abolishing gene expression. Homozygotes are viable and fertile. CD27 is a tumor necrosis factor (TNF) receptor family member that in mice is found on hematopoietic stem cells in bone marrow, thymocytes, naive and activated peripheral T cells, subsets of natural killer (NK) cells and activated B cells. CD27 expression can be lost from effector T cells and is absent from IL-17-producing gamma delta T cells. CD27 is not expressed outside of the lymphoid lineage. Upon binding of its ligand, CD70, on activated immune cells, CD27 drives clonal expansion of primed T cells in lymphoid organs and survival of effector T cells in non-lymphoid organs. CD27-deficient mice have a more narrow responder TCR repertoire to antigenic challenge. CD27 also supports effector function of T cells and NK cells and memory formation and function of T cells. CD27-deficient mice have normal conventional T cell and B cell development, but a mildly impaired regulatory T cell development. They have mild to moderate impairments in primary and particularly memory T cell responses to viruses, dependent on the virus type or strain. In the mouse, B cell function is not overtly affected by CD27-deficiency. In the mouse, activated immune cells bearing CD70 can exert feed-back control on hematopoiesis via CD27 on hematopoietic precursors.

Development

A targeting vector was designed to replace the coding region of the CD27 antigen (Cd27) gene with a hygromycin resistance (hygro) cassette. The construct was electroporated into 129P2/OlaHsd-derived E14IB10 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to FVB females to generate a colony of Cd27^-/- mice. These mice were backcrossed to C57BL/6 for at least 8 generations (see SNP note below). Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Please note the Cd27 locus is linked to the Ly49 locus and these mice have retained the 129 Ly49 allotype.

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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. One of the 43 markers throughout the genome were segregating with 129. One marker was segregating with FVB, likely a passenger segment for Cd27 mutation. Also, all 4 of the 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 C57BL/6N genetic background.

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Hendriks J; Gravestein LA; Tesselaar K; van Lier RA; Schumacher TN; Borst J. 2000. CD27 is required for generation and long-term maintenance of T cell immunity. Nat Immunol 1(5):433-40PubMed: 11062504 MGI: J:65516

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Genetics

Cd27^tm1Jbo

Allele Symbol: Cd27^tm1Jbo

Allele Name	targeted mutation 1, Jannie Borst
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	CD27-; Tnfrsf7^-
Gene Symbol and Name	Cd27, CD27 antigen
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	6
Molecular Note	The entire coding region of the gene was replaced with a PGK-hygro cassette via homologous recombination. Immunofluorescence flow cytometry of spleen cells from homozygous mutant animals confirmed the absence of protein expression.

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
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
- Inflammation

Mammalian Phenotype Terms by Genotype

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

Genotype: Cd27^tm1Jbo/Cd27^tm1Jbo
B6.129P2-Cd27

cellular phenotype

increased T cell apoptosis
- cultured Treg cells show significantly higher apoptosis than WT cells but other T cell populations do not

mammalian phenotype

immune system phenotype
- Normal - CD4+ve Foxp3-ve T cell (pre-Treg) numbers in thymus and spleen are comparable to controls; immature thymocyte populations and CD4-ve CD8+ve populations in thymus and spleen are similar to contols

hematopoietic system phenotype

decreased regulatory T cell number
- frequency and absolute number of CD4+ve Foxp3+ve T (Treg) cells is reduced in adult mice
- frequency and absolute number of CD4+ve Foxp3+ve T cells in thymi of neonates is reduced compared to WT
- treatment with neutralizing antibodies to CD80/CD86 drastically reduces number of Treg cells in the thymus; CD28 signaling blockade reduces number of thymic pre-Treg (CD4+Foxp3-CD25+) cells

increased T cell apoptosis
- cultured Treg cells show significantly higher apoptosis than WT cells but other T cell populations do not

increased leukocyte cell number
- slightly higher numbers of all white cell lineages in the peripheral blood

abnormal leukopoiesis
- increased capacity to generate myeloid colonies but depressed leukocyte differentiation

immune system phenotype

decreased regulatory T cell number
- frequency and absolute number of CD4+ve Foxp3+ve T (Treg) cells is reduced in adult mice
- frequency and absolute number of CD4+ve Foxp3+ve T cells in thymi of neonates is reduced compared to WT
- treatment with neutralizing antibodies to CD80/CD86 drastically reduces number of Treg cells in the thymus; CD28 signaling blockade reduces number of thymic pre-Treg (CD4+Foxp3-CD25+) cells

increased T cell apoptosis
- cultured Treg cells show significantly higher apoptosis than WT cells but other T cell populations do not

abnormal leukopoiesis
- increased capacity to generate myeloid colonies but depressed leukocyte differentiation

increased leukocyte cell number
- slightly higher numbers of all white cell lineages in the peripheral blood

Genotype: Cd27^tm1Jbo/Cd27^tm1Jbo
either: B6.129P2-CD27 or 129P2/OlaHsd-Tnfrsf7

immune system phenotype

abnormal cytotoxic T cell physiology
- percentage of influenza virus specific CD8+ cells are reduced in the spleen
- delayed CD8+ memory response
- absolute numbers of influenza virus specific CD8+ cells are reduced in the lung

abnormal T cell physiology
- thymidine incorporation in T cells exposed to CD3epsilon antibody reduced 1.8x, probably due to reduced survival
- reduced memory response
- lower response of both CD4+ and CD8+ single positive cells to influenza virus

abnormal CD4-positive, alpha-beta T cell physiology
- delayed memory response by about 2 days

hematopoietic system phenotype

abnormal cytotoxic T cell physiology
- delayed CD8+ memory response
- absolute numbers of influenza virus specific CD8+ cells are reduced in the lung
- percentage of influenza virus specific CD8+ cells are reduced in the spleen

abnormal T cell physiology
- lower response of both CD4+ and CD8+ single positive cells to influenza virus
- thymidine incorporation in T cells exposed to CD3epsilon antibody reduced 1.8x, probably due to reduced survival
- reduced memory response

abnormal CD4-positive, alpha-beta T cell physiology
- delayed memory response by about 2 days

References

Hendriks J; Gravestein LA; Tesselaar K; van Lier RA; Schumacher TN; Borst J. 2000. CD27 is required for generation and long-term maintenance of T cell immunity. Nat Immunol 1(5):433-40PubMed: 11062504 MGI: J:65516

Additional - Cd27^tm1Jbo related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Cd27
- 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 B6.129P2(FVB)-Cd27^tm1Jbo/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019009 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 wildtype for Cd27<tm1Jbo>

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

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Cd27tm1Jbo

Allele Symbol: Cd27tm1Jbo

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Cd27tm1Jbo/Cd27tm1JboB6.129P2-Cd27

cellular phenotype

mammalian phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Cd27tm1Jbo/Cd27tm1Jboeither: B6.129P2-CD27 or 129P2/OlaHsd-Tnfrsf7

immune system phenotype

hematopoietic system phenotype

References

Additional - Cd27tm1Jbo 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

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Cd27^tm1Jbo

Allele Symbol: Cd27^tm1Jbo

Genotype: Cd27^tm1Jbo/Cd27^tm1Jbo
B6.129P2-Cd27

Genotype: Cd27^tm1Jbo/Cd27^tm1Jbo
either: B6.129P2-CD27 or 129P2/OlaHsd-Tnfrsf7

Additional - Cd27^tm1Jbo related