B6.129P2(C)-Ccr7^tm1Rfor/J

Stock number: 006621
Product name: CCR7-
Research areas: Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

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.

Detailed description

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.

Development

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

Symbol: Ccr7^tm1Rfor
Name: targeted mutation 1, Reinhold Forster
MGI accession ID: MGI:2180679
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ccr7
Marker name: chemokine (C-C motif) receptor 7
Chromosome: 11
Strain of origin: 129P2/OlaHsd
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.