B6.129S-Ccr1^tm1Gao/AdlJ

Stock number: 032932
Product name: CCR1 KO

Research areas: Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

Ccr1 knock-out mice may be useful in studying leukocyte recruitment and adhesion, as well as susceptibility to viruses and parasites.

Detailed description

The targeted Ccr1 gene encodes a beta (or CC) chemokine receptor which is expressed mainly on hematopoietic cells and binds chemokines Ccl3 (MIP-1alpha), Ccl5 (RANTES), Ccl6, Ccl7, Ccl8, and Ccl9. These Ccr1 KO mice carry a knock-out allele of the Ccr1 gene with a neo cassette replacing 352bp of the ORF (encoding 33% of the protein: third to the fifth transmembrane segment). Homozygotes are viable and fertile. Homozygotes exhibit reduced leukocyte recruitment and adhesion after experimentally induced myocardial infarction. Homozygotes are more susceptible to fungal infection (Aspergillus fumigatus). In response to intravenous injection of Schistosoma mansoni eggs, homozygotes develop smaller lung granulomas compared to wildtype controls. Orthodontic tooth movement and bone remodeling is reduced in homozygotes with fewer TRAP-positive osteoclasts observed compared to wildtype controls.

Development

A targeting vector containing a neo cassette was used to disrupt 352bp of the ORF (encoding 33% of the protein: third to the fifth transmembrane segment) of the Ccr1 gene. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were bred to C57BL/6 mice. Heterozygotes were intercrossed to generate homozygotes. The mice were then backcrossed to C57BL/6NAi mice for 10 generations. Due to contamination of the C57BL/6NAi strain by the Ifng^tm1Ts knock-out allele, the mice were then backcrossed to C57BL/6NTac for 5 generations by the donating lab to remove the mutant Ifng allele. In addition, the donating investigator reports that although these mice harbor no additional mutant loci, they may contain incidental genetic background contributions as a result of past matings with other mutant mouse strains (see SNP note below). Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).



In 2019 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 on Chormosome 18 was segregating with 129. Also, 1 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.

Allele

Symbol: Ccr1^tm1Gao
Name: targeted mutation 1, Ji-Liang Gao
MGI accession ID: MGI:1931850
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: CCR1-
Marker symbol: Ccr1
Marker name: chemokine (C-C motif) receptor 1
Marker synonyms: CD191; CKR1; CKR-1; Cmkbr1; HM145; MIP1aR; SCYAR1
Chromosome: 9
Strain of origin: 129S4/SvJae
Molecular note: A neomycin resistance cassette replaced open reading frame sequences that correspond to 33% of the protein, from the third to the fifth transmembrane segment. Transcript was not detected in neutrophils of homozygous mutant animals.