BXSB.129S2(Cg)-Cxcr5^tm1Lipp/DcrJ

Stock number: 021874
Product name: CXCR5-
Strain synonyms: BXSB.Yaa Cxcr5-/-, BXSB.Cxcr5-/-
Research areas: Cell Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Research Tools, Virology Research

Description

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.

Detailed description

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.

Development

The CXCR5 null allele (Cxcr5^tm1Lipp) 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

Symbol: Cxcr5^tm1Lipp
Name: targeted mutation 1, Martin Lipp
MGI accession ID: MGI:2158677
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cxcr5
Marker name: chemokine (C-X-C motif) receptor 5
Chromosome: 9
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.