CXCR5-deficient BXSB.Yaa mice (BXSB.Cxcr5-/- or BXSB.Yaa Cxcr5-/-) are a BXSB-congenic strain carrying a null mutation of the chemokine (C-X-C motif) receptor 5 gene. The chemokine receptor-deficiency of BXSB.Cxcr5-/- mice significantly delays manifestation of the spontaneous lupus-like autoimmune syndrome observed for BXSB/MpJ inbred mice. These BXSB.Cxcr5-/- mice may be useful in studying the function of T-follicular helper (Tfh) cells in B-cell affinity maturation, class switch recombination, and plasma and memory B-cell generation within the germinal center, as well as their role in autoimmune disease.
Dr. Derry Roopenian, The Jackson Laboratory
CXCR5-deficient BXSB.Yaa mice (BXSB.Cxcr5-/- or BXSB.Yaa Cxcr5-/-) are a BXSB-congenic strain carrying a null mutation of the chemokine (C-X-C motif) receptor 5 gene. Endogenous expression of the CXCR5 chemokine receptor on activated T cells facilitates its own maturation into T-follicular helper (Tfh) cells, as well as B cell commitment in the germinal center.
BXSB/MpJ inbred males (Stock No. 000740) develop a spontaneous lupus-like autoimmune syndrome: mortality starts at ~13 weeks of age with 50% lethality by ~30 weeks and 76% lethality by ~40 weeks. BXSB/MpJ inbred females develop a greatly attenuated form of autoimmune disease because they lack Yaa.
Homozygous (Cxcr5-/-) mice are viable and fertile. Compared to BXSB/MpJ, the chemokine receptor-deficiency of BXSB.Cxcr5-/- mice significantly delays manifestation of the autoimmune phenotype in both males and females. Specifically, mortality in males starts at ~16 weeks of age with 67% still alive at ~40 weeks of age.
Heterozygous males (BXSB.Cxcr5+/-) develop the BXSB/MpJ autoimmune phenotype. Heterozygous females develop a greatly attenuated form of autoimmune disease because they lack Yaa.
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 of BXSB.Cxcr5-/- mice could vary from that originally described for CXCR5-deficiency on other genetic backgrounds. We will modify the strain description if necessary as published results become available. C57BL/6J-congenic mice harboring this CXCR5 null allele are described and available from The Jackson Laboratory Repository as Stock No. 006659. C57BL/6J-congenic homozygous mice exhibit a complex pattern of lymph node developmental defects (e.g. deficient in inguinal, iliac and parathymic lymph nodes). CXCR5-deficient mice show a completely disorganized splenic microarchitecture, lacking segregated T- and B-cell areas within the splenic white pulp.
The CXCR5 null allele (Cxcr5tm1Lipp) was designed by Dr. Martin Lipp (Max-Delbruck-Center for Molecular Medicine) to replace the 350 bp coding region of exon 2 of the chemokine (C-X-C motif) receptor 5 gene on chromosome 9 with a neomycin resistance cassette. C57BL/6J-congenic mice harboring this CXCR5 null allele are described and available from The Jackson Laboratory Repository as Stock No. 006659.
Dr. Derry C. Roopenian (The Jackson Laboratory) obtained some of these mutant mice and backcrossed them with BXSB/MpJ inbred mice (Stock No. 000740) for 11 generations, and then maintained the colony by breeding homozygous mice together. In 2013, Dr. Roopenian sent some BXSB.Cxcr5-/- mice at generation N11F7 to The Jackson Laboratory Repository (Autoimmune Resource) to establish Stock No. 021874. Male mice have the BXSB/MpJ-derived Y chromosome that contains the Y-linked autoimmune accelerator locus (Yaa).
|Allele Name||targeted mutation 1, Martin Lipp|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Martin Lipp; Cxcr5tm1Lipp|
|Gene Symbol and Name||Cxcr5, chemokine (C-X-C motif) receptor 5|
|Gene Synonym(s)||Gpcr6; Burkitt lymphoma receptor 1; CXCR-5; BLR1; Gpcr6; G-protein coupled receptor 6; NLR; CD185; MDR15; Blr1; Blr1|
|Strain of Origin||129S2/SvPas|
|Molecular Note||A neomycin selection cassette was inserted into exon 2. Northern blot analysis on RNA derived from spleen cells of homozygous mice demonstrated that no detectable transcipt was produced from this allele (data not shown), and flow cytometry experiments on leukocytes derived from homozygous mice demonstrated that no detectable protein was produced.|
|Mutations Made By|| |
Martin Lipp, Max-Delbrueck-Center
To maintain the live colony, homozygous mice may be bred together. Homozygous animals of both sexes have delayed onset of the spontaneous lupus-like autoimmune syndrome observed for BXSB/MpJ inbred mice (Stock No. 000740). Specifically, BXSB.Cxcr5-/- males have only 33% lethality at ~40 weeks of age. Homozygous females develop a greatly attenuated form of autoimmune disease because they lack Yaa. Heterozygotes will develop the sex-specific autoimmune phenotype of BXSB/MpJ. The expected coat color is white-bellied agouti.
When using the CXCR5- mouse strain in a publication, please cite the originating article(s) and include JAX stock #021874 in your Materials and Methods section.
|Heterozygous for Cxcr5<tm1Lipp>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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