These Cxcr4 knock-out mice exhibit a reduction of B-lymphopoiesis, lack of bone marrow myelopoiesis, and a vascularization defect.
IMR Colony, The Jackson Laboratory
Mice that are homozygous null for the Cxcr4 gene die perinatally, with ~30% dying by embryonic day 18.5. Viable embryos are slightly smaller than wild type mice and exhibit vascular congestion in the kidneys, interstitial hemorrhages, and abnormalities in bone marrow and cerebellum. Homozygote embryos also show reduced B-lymphopoiesis, reduced myelopoiesis in fetal liver and an absence of myelopoiesis in bone marrow. Histological examination reveals a distorted architecture in the tissues if the cerebellum, featuring an attenuated external granule cell layer and an ectopic placement of Purkinje cells.
Cxcr4 encodes a receptor commonly called CXCR4, the ligand of which is the chemokine stromal cell-derived factor 1 (SDF-1), an important regulator of hematopoietic cell development, migration and proliferation. CXCR4 also functions as a coreceptor for the entry of T-tropic strains of HIV-1 into CD4+ T cells.
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. This is the case for the strain above. 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 containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt exon 2 which codes the fourth transmembrane domain. The construct was electroporated into 129X1/SvJ-derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric mice were crossed to C57BL/6J animals.
|Allele Name||targeted mutation 1, Qing Ma|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Cxcr4, chemokine (C-X-C motif) receptor 4|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A PGK-neomycin resistance cassette replaced sequences in exon 2 that encode the fourth transmembrane domain and a portion of the third extracellular domain. RT-PCR studies did not detect transcript in homozygous brain.|
|Mutations Made By|| |
Qing Ma, Boston Children's Hospital
This strain originated on a B6;129X background and has been backcrossed to C57BL/6 for at least eight generations (2/03). Homozygous mice die perinatally. Coat color expected from breeding:Black
When using the CXCR4- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004341 in your Materials and Methods section.