B6.Cg-Ackr3^tm1Fma/J

Stock number: 033828
Product name: Cxcr7^lox
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

Cxcr7^lox/lox mice possess loxP sites flanking exon 2 of the atypical chemokine receptor 3 (Ackr3) gene. This strain may be useful in immunological studies as well as studies of cardiac development and cancer.

Detailed description

Cxcr7^lox/lox mice possess loxP sites flanking exon 2 of the atypical chemokine receptor 3 (Ackr3) gene. The floxed region also includes a neomycin resistance cassette. CXCR7 encodes an atypical chemokine receptor expressed in some T cell subsets, and NK cells, as well as in B cells, with highest expression in human memory B cell subsets, mouse splenic marginal zone (MZ) B cells and in transitional type 2 MZ precursors. It has also been implicated in the migration of neuroendocrine cells, specifically of gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus that play an essential role in mammalian reproduction. Recently, CXCR7 has been found to be overexpressed in a variety of tumors. Mice that are homozygous for this floxed allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 2 deleted in the cre-expressing tissues.

When bred to CMV-Cre mice (Stock No. 006054), resulting Cxcr7^-/- mutants die within 24 hours of birth with ventricular septal defects and semilunar heart valve (SLV) malformation. They also exhibit defects in the expression of factors essential for valve formation, vessel protection, and endothelial cell growth and survival. Cxcr7^lox/lox mice bred to TIE2cre mice (Stock No. 004128), to specifically delete Cxcr7 in the vascular endothelium, recapitulated this phenotype, albeit with milder effects and partial penetrance.

C57BL/6 mice are natural null mutants for Cxcl11, one of only two chemokine ligands of CXCR7, because a 2-bp insertion soon after the start codon creates a premature stop codon. Because C57BL/6 mice develop normally in the absence of a functional copy of Cxcl11, CXCL11/CXCR7 interaction is likely to play a redundant role in SLV formation.

Development

The Cxcr7^lox targeting vector was designed to insert a loxP site upstream of exon 1 and a neomycin selection cassette followed by a second loxP site downstream of exon 2 of the atypical chemokine receptor 3 (Ackr3) gene. The construct was electroporated into B6.Cg-Thy1^a-derived Bruce 4 embryonic stem (ES) cells and correctly targeted ES cells were injected into BALB/c blastocysts. The resulting chimeric males were bred with C57BL/6J females, and progeny were bred to CMV-Cre mice (Stock No. 006054) for a few generations. Following SNP analysis, mice that were 99.8% C57BL/6 were sent to The Jackson Laboratory. 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). The cre-expressing transgene was bred out of the colony.

Allele

Symbol: Ackr3^tm1Fma
Name: targeted mutation 1, Fabienne Mackay
MGI accession ID: MGI:3722943
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Cxcr7^lox
Marker symbol: Ackr3
Marker name: atypical chemokine receptor 3
Marker synonyms: CMKOR1; CXCR7; CXC-R7; CXCR-7; GPR159; RDC1; RDC-1
Chromosome: 1
Strain of origin: B6.Cg-Thy1^a
Molecular note: LoxP sites were inserted around exon 2.