B6N.129S2(Cg)-Ccl25^tm1.1Mal/J

Stock number: 016938
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research

Description

These knockout mice lack a portion of exon 2 and all of exons 3-4 of the chemokine (C-C motif) ligand 25 (Ccl25) gene. These mice may be useful for studying gut-specific lymphocyte trafficking and early T cell development.

Detailed description

In this strain part of exon 2, encoding the ATG initiation codon, and exons 3-4 of the chemokine (C-C motif) ligand 25 (Ccl25) gene were removed. Homozygotes are viable, fertile, and normal in size. CCL25 is a thymus-expressed chemokine which plays a role in T cell development, and thymocyte, macrophage, and dendritic cell migration. Also highly expressed in epithelial cells lining the villi of the small intestines, CCL25, with its receptor, CCR9, is involved in the generation of gut-specific lymphocyte trafficking. These CCL25 deficient mice exhibit a 1.5-fold increase in CCR9 expression on the surface of thymocytes. They contain fewer lymphocytes in the epithelium, fewer CD8 T cells in the lamina propria (LP) of the small intestines, and exhibit an increase in CD4 T cells in the LP. Mature, antigen-specific naive T cells transferred into these mice fail to migrate to the LP or the epithelium of the small intestines.

Development

The Ccl25^-/- targeting vector was designed to replace part of exon 2, encoding the ATG initiation codon, and exons 3-4 of the chemokine (C-C motif) ligand 25 (Ccl25) gene with a loxP-flanked neomycin (neo) resistance cassette. This construct was injected into 129S2/SvPas-derived CK35 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred with Tg(CMV-cre)1Cgn mice to delete the floxed-neo cassette. The resulting mice were then backcrossed to C57BL/6N mice (see SNP note below) for at least 15 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation.

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 the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 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.

Allele

Symbol: Ccl25^tm1.1Mal
Name: targeted mutation 1.1, Bernard Malissen
MGI accession ID: MGI:3797365
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ccl25
Marker name: chemokine (C-C motif) ligand 25
Chromosome: 8
Strain of origin: 129S2/SvPas
Molecular note: Part of exon 2 (including the translation initiation site) and all of exons 3 and 4 were replaced with a floxed neomycin resistance gene cassette. The neo cassette was removed through subsequent germline, cre-mediated recombination.