Overview

Also Known As:BXSB.Yaa Cxcr5-/-, BXSB.Cxcr5-/-, CXCR5-

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.

Donating Investigator

Derry Roopenian, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Cxcr5^tm1Lipp

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Cxcr5	chemokine (C-X-C motif) receptor 5

View Genetics

Research Applications

Research Tools
Hematological Research
Immunology, Inflammation and Autoimmunity Research
Mouse/Human Gene Homologs
Virology Research
Cell Biology Research
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

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).

Control Suggestions

000740 BXSB/MpJ

Additional Information

Considerations for Choosing Controls

Genetics

Cxcr5^tm1Lipp

Allele Symbol: Cxcr5^tm1Lipp

Allele Name	targeted mutation 1, Martin Lipp
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Blr1^-; CXCR5-
Gene Symbol and Name	Cxcr5, chemokine (C-X-C motif) receptor 5
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	9
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

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - B cell deficiency
  - production of B cells and antibodies
  - B and T cell deficiency
  - T cell deficiency
  - T cell deficiency, xenograft/transplant host
  - T cell specific surface marker
  - specific T cell deficiency
  - genes regulating susceptibility to infectious disease and endotoxin
- Toxicology Research
  - B and T cell deficiency, xenograft transplant host
- Genetics Research
  - Tissue/Cell Markers: T cell specific surface marker
Hematological Research
- Immunological Defects
  - B and T cell deficiency
Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - B and T cell deficiency
  - lupus erythematosus, control
  - lupus erythematosus
  - B cell deficiency
- Immunodeficiency
  - B cell defects
  - B cell deficiency
  - B and T cell deficiency
  - T cell deficiency
  - specific T cell deficiency
  - multiple immune defects
  - defects in humoral immune responses
- Intracellular Signaling Molecules
- Growth Factors/Receptors/Cytokines
- Inflammation
  - B and T cell deficiency
- Lymphoid Tissue Defects
  - B and T cell deficiency
  - Lymphocyte Homing
Mouse/Human Gene Homologs
- systemic lupus erythematosus
Virology Research
- B and T Cell Deficiency
Cell Biology Research
- Signal Transduction
Internal/Organ Research
- Thymus Defects
  - B and T cell deficient
- Lymphoid Tissue Defects
  - B and T cell deficiency
  - T cell deficiency

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Cxcr5^tm1Lipp/Cxcr5^tm1Lipp
involves: 129S2/SvPas * CD-1

immune system phenotype

abnormal spleen primary B follicle morphology
- at 8 wks of age, homozygotes display defective formation of primary splenic follicles, including: the T cell zone is located centrally but not polarized in the follicle; the T cell zone is completely surrounded by a small rim of B cell-expressing IgD but not IgM (i.e. IgM⁺IgD⁺ subset is absent); a prominent marginal zone surrounds the follicle completely
- not IgM (i.e. IgM⁺IgD⁺ subset is absent); a prominent marginal zone surrounds the follicle completely

absent cervical lymph nodes

absent inguinal lymph nodes
- homozygotes lack inguinal lymph nodes

absent spleen germinal center
- despite high numbers of germinal center founder cells, no functional germinal centers develop in mutant spleen after immunization with the T cell-dependent antigen DNP-KHL

increased B cell number
- homozygotes display a 2- to 4-fold increase in spleen or peripheral blood cells co-expressing B220 and high amounts fo IgM

abnormal spleen secondary B follicle morphology

absent Peyer's patches
- 55% (42 of 76) of homozygotes show complete absence of Peyer's patches

abnormal Peyer's patch morphology
- ~30% (26 of 76) of homozygotes exhibit 1-4 small and rudimentary structures resembling Peyer's patches
- ~16% (12 of 76) of homozygotes exhibit normally sized Peyer's patches with multiple B and T cell-rich zones instead of the large follicles present in wild-type mice

abnormal leukocyte migration
- homozygotes exhibit a severely impaired lymphocyte migration to the Peyer's pathces and the B cell follicles of the spleen, resulting in morphologically abnormal primary lymphoid follicles
- activated B cells fail to migrate from the T cell-rich zone into B cell follicles of the spleen

absent lymph nodes
- absence of inguinal, iliac/periaortic, axillary, branchial, deep cervical, sacral/caudal, and parathymic lymph nodes

absent axillary lymph nodes

absent brachial lymph nodes

absent follicular dendritic cells
- absence of primary follicular dendritic cells

cellular phenotype

abnormal leukocyte migration
- homozygotes exhibit a severely impaired lymphocyte migration to the Peyer's pathces and the B cell follicles of the spleen, resulting in morphologically abnormal primary lymphoid follicles
- activated B cells fail to migrate from the T cell-rich zone into B cell follicles of the spleen

hematopoietic system phenotype

abnormal spleen primary B follicle morphology
- at 8 wks of age, homozygotes display defective formation of primary splenic follicles, including: the T cell zone is located centrally but not polarized in the follicle; the T cell zone is completely surrounded by a small rim of B cell-expressing IgD but not IgM (i.e. IgM⁺IgD⁺ subset is absent); a prominent marginal zone surrounds the follicle completely
- not IgM (i.e. IgM⁺IgD⁺ subset is absent); a prominent marginal zone surrounds the follicle completely

abnormal spleen secondary B follicle morphology

increased B cell number
- homozygotes display a 2- to 4-fold increase in spleen or peripheral blood cells co-expressing B220 and high amounts fo IgM

abnormal leukocyte migration
- homozygotes exhibit a severely impaired lymphocyte migration to the Peyer's pathces and the B cell follicles of the spleen, resulting in morphologically abnormal primary lymphoid follicles
- activated B cells fail to migrate from the T cell-rich zone into B cell follicles of the spleen

absent spleen germinal center
- despite high numbers of germinal center founder cells, no functional germinal centers develop in mutant spleen after immunization with the T cell-dependent antigen DNP-KHL

References

Additional - Cxcr5^tm1Lipp related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Cxcr5
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous for Cxcr5<tm1Lipp>

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Frozen Mouse Embryo	BXSB.129S2(Cg)-Cxcr5<tm1Lipp>/DcrJ Frozen Embryos	$3373.50

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:BXSB.Yaa Cxcr5-/-, BXSB.Cxcr5-/-, CXCR5-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Cxcr5tm1Lipp

Allele Symbol: Cxcr5tm1Lipp

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Cxcr5tm1Lipp/Cxcr5tm1Lippinvolves: 129S2/SvPas * CD-1

immune system phenotype

cellular phenotype

hematopoietic system phenotype

References

Additional - Cxcr5tm1Lipp related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Cxcr5^tm1Lipp

Allele Symbol: Cxcr5^tm1Lipp

Genotype: Cxcr5^tm1Lipp/Cxcr5^tm1Lipp
involves: 129S2/SvPas * CD-1

Additional - Cxcr5^tm1Lipp related