Homozygous mice show delayed primary B or T cell immune responses. Lymph nodes from homozygous mice are devoid of naive T cells and dendritic cells, and secondary lymph organs exhibit morphological abnormalities. These mutant mice may be useful in immunological studies of chemokine receptors, including T- and B-cell function in primary and adaptive immune responses, entry of lymphocytes and dendritic cells into secondary lymphoid organs, alloimmune responses, and the development of transplant rejection.
Martin Lipp, Max-Delbrueck-Center
Genetic Background | Generation |
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N9+N2F6
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Ccr7 | chemokine (C-C motif) receptor 7 |
Homozygous mice are viable and fertile and show delayed primary B or T cell immune responses. Lymph nodes from homozygous mice are devoid of naive T cells and dendritic cells (DCs), but the T cell populations in the blood, the red pulp of the spleen, and in the bone marrow are greatly expanded. Secondary lymph organs exhibit morphological abnormalities, and adoptive transfer experiments demonstrate impaired B- and T-cell migration. In a model of acute allogeneic tumor rejection, homozygous mice fail to reject subcutaneously injected MHC class I mismatched tumor cells, and cytotoxic activity of allospecific T cells is severely compromised. These mutant mice (along with CXCR5-deficient mice - Stock No. 006659) - may be useful in immunological studies of chemokine receptors, including T- and B-cell function in primary and adaptive immune responses, entry of lymphocytes and dendritic cells into secondary lymphoid organs (and their homing to T- and B-cell zones therein), alloimmune responses, and the development of transplant rejection.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector was designed to replace a fragment of the third exon of the targeted gene (encompassing amino acids Ser-139 to Asp-309) with a neomycin resistance gene. The construct was electroporated into 129P2/OlaHsd-derived E14K embryonic stem (ES) cells, and correctly targeted ES cells were injected into BALB/c blastocysts. Chimeric males were bred to BALB/c. Mutant mice were backcrossed to C57BL/6 mice for 8 generations prior to arrival at The Jackson Laboratory. These mice were maintained on a mixed C57BL/6J ; C57BL/6NJ congenic background. 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).
In 2015, a 32 SNP (single nucleotide polymorphism) panel with markers on 14 of 19 chromosomes, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed. This revealed 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating.
Allele Name | targeted mutation 1, Reinhold Forster |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | CCR7- |
Gene Symbol and Name | Ccr7, chemokine (C-C motif) receptor 7 |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 11 |
Molecular Note | 0.5 kb of exon 3 encoding serine 139 to aspartic acid 309 was disrupted by insertion of a neomycin resistance cassette via homologous recombination. Successful targeting was verified in homozygous mutant animals by Southern blot analysis and chemotaxis assays. Spleen cells from homozygous animals demonstrated lack of chemotactic response towards EBI-1 ligand chemokine (ELC), a known ligand of the targeted gene. |
Mutations Made By | Martin Lipp, Max-Delbrueck-Center |
When maintaining a live colony, homozygous mice are bred.
When using the CCR7- mouse strain in a publication, please cite the originating article(s) and include JAX stock #006621 in your Materials and Methods section.
Service/Product | Description | Price |
---|---|---|
Heterozygous for Ccr7<tm1Rfor> |
Frozen Mouse Embryo | B6.129P2(C)-Ccr7<tm1Rfor>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129P2(C)-Ccr7<tm1Rfor>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129P2(C)-Ccr7<tm1Rfor>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129P2(C)-Ccr7<tm1Rfor>/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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