Overview

Also Known As:BXSB.Yaa/Il21r-KO

IL-21R-deficient BXSB.Yaa mice (BXSB.Yaa/Il21r-/- or BXSB.Yaa Il21r-/-) are a BXSB/MpJ-congenic strain carrying a null mutation of the interleukin 21 receptor. The IL-21 signaling deficiency of BXSB-Yaa/Il21r-/- mice prevents the humoral, leukocytic, and kidney manifestations of the spontaneous lupus-like autoimmune syndrome observed for BXSB/MpJ inbred mice. These BXSB-Yaa/Il21r-/- mice may be useful in studying the role of IL-21 signaling in autoimmune disease.

Donating Investigator

Dr. Derry Roopenian, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Yaa

Allele Type	Gene Symbol	Gene Name
Spontaneous	Yaa	accelerated autoimmunity and lymphoproliferation transposition

Il21r^tm1Wjl

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Il21r	interleukin 21 receptor

View Genetics

Research Applications

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

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

IL-21R-deficient BXSB.Yaa mice (BXSB.Yaa/Il21r-/- or BXSB.Yaa Il21r-/-) are a BXSB/MpJ-congenic strain carrying a null mutation of the interleukin 21 receptor.

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 (IL-21R-/-) mice are viable and fertile with normal lifespan. Homozygotes lack IL-21 signaling and have decreased immunoglobulin levels, decreased Th17 T cell differentation, and decreased production of IL-17. Compared to BXSB/MpJ, the IL-21 signaling-deficiency of BXSB.Yaa/Il21r-/- mice prevents the humoral, leukocytic, and kidney manifestations of the spontaneous autoimmune syndrome in both males and females.

Heterozygous males (BXSB.Yaa/IL-21R+/-) develop the BXSB/MpJ autoimmune phenotype. Heterozygous females develop a greatly attenuated form of autoimmune disease because they lack Yaa.

Development

The IL-21R null allele (Il21r^tm1Wjl) was designed by Dr. Warren J. Leonard (National Institutes of Health) with a neomycin resistance cassette replacing several coding exons of the Il21r gene (interleukin 21 receptor) on chromosome 7. Specifically, the sequences encoding the signal peptide through the transmembrane domain were deleted (only 5 amino acids of the signal peptide were retained); this results in a frameshift mutation of the cytoplasmic domain encoding sequence. The targeting vector was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred to wildtype animals to obtain germline transmitting founder mice. In 2004, IL-21R mutant mice backcrossed six generations onto BALB/c were sent to Dr. Derry C. Roopenian (The Jackson Laboratory). There, they were bred with C57BL/6 for at least one generation. Next, the mutant mice were backcrossed with BXSB/MpJ inbred mice (Stock No. 000740) for 11 generations, and then maintained by breeding homozygous mice together. In 2013, Dr. Roopenian sent some BXSB.Yaa/Il21r-/- mice at generation N11F18 to The Jackson Laboratory Repository (Autoimmune Resource) to establish Stock No. 021568. 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

Selected References

Bubier JA; Sproule TJ; Foreman O; Spolski R; Shaffer DJ; Morse HC 3rd; Leonard WJ; Roopenian DC. 2009. A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice. Proc Natl Acad Sci U S A 106(5):1518-23PubMed: 19164519 MGI: J:144484
McPhee CG; Sproule TJ; Shin DM; Bubier JA; Schott WH; Steinbuck MP; Avenesyan L; Morse HC 3rd; Roopenian DC. 2011. MHC class I family proteins retard systemic lupus erythematosus autoimmunity and B cell lymphomagenesis. J Immunol 187(9):4695-704PubMed: 21964024 MGI: J:179430
Ozaki K; Spolski R; Feng CG; Qi CF; Cheng J; Sher A; Morse HC 3rd; Liu C; Schwartzberg PL; Leonard WJ. 2002. A critical role for IL-21 in regulating immunoglobulin production. Science 298(5598):1630-4PubMed: 12446913 MGI: J:80474

View All References

Genetics

Yaa

Allele Symbol: Yaa

Allele Name	accelerated autoimmunity and lymphoproliferation
Allele Type	Spontaneous
Allele Synonym(s)	Is(XOfd1-Mid1;Y)1Mp; Tp(X;Y)1Ekw
Gene Symbol and Name	Yaa, accelerated autoimmunity and lymphoproliferation transposition
Gene Synonym(s)
Strain of Origin	SB/Le
Chromosome	Y
Molecular Note	An approximately 4 MB region of the X chromosome that includes at least 13 known genes (spanning from Ofd1 to Mid1) was translocated to the Y chromosome adjacent to the pseudoautosomal region. Increased RNA expression of Msl3, Tlr7, Tmsb4x and Rab9 was detected in follicular B cells.

Il21r^tm1Wjl

Allele Symbol: Il21r^tm1Wjl

Allele Name	targeted mutation 1, Warren J Leonard
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	IL-21R^-
Gene Symbol and Name	Il21r, interleukin 21 receptor
Gene Synonym(s)
Strain of Origin	129
Chromosome	7
Molecular Note	The endogenous locus was disrupted by the insertion of a neomycin selection cassette. Sequence encoding the majority of the signal peptide through the transmembrane domain was replaced by neo, resulting in a frameshift mutation affecting sequence encoding the cytoplasmic domain. Transcript was undetected by RT-PCR analysis of thymocytes obtained from homozygous mutant mice.

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
  - B cell specific marker
  - T cell deficiency
  - T cell deficiency, xenograft/transplant host
  - specific T cell deficiency
  - B, T, and NK cell deficiency
  - T cell specific surface marker
  - B cell specific surface marker
  - production of B cells and antibodies
  - B and T cell deficiency
  - NK Cell Deficiency
- Genetics Research
  - Tissue/Cell Markers: B cell specific marker
  - Tissue/Cell Markers: T cell specific surface marker
- Toxicology Research
  - B and T cell deficiency, xenograft transplant host
- Cancer Research
  - B, T, and NK cell deficiency, xenograft/transplant host
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - T cell deficiency
  - specific T cell deficiency
  - B cell deficiency
  - B, T, and NK cell deficiency
  - NK Cell Deficiency
  - NK Cell and Cd8 T Cell defects
  - B and T cell deficiency
  - B cell defects
  - defects in humoral immune responses
- Inflammation
  - B and T cell deficiency
- Lymphoid Tissue Defects
  - B and T cell deficiency
  - hematopoietic development
- Autoimmunity
  - B and T cell deficiency
  - B cell deficiency
  - lupus erythematosus, control
  - lupus erythematosus
- Intracellular Signaling Molecules
- Growth Factors/Receptors/Cytokines
Virology Research
- B and T Cell Deficiency
Developmental Biology Research
- Internal/Organ Defects
  - hematopoietic defects
  - Lymphoid Tissue Defects
- Lymphoid Tissue Defects
  - hematopoietic defects
Hematological Research
- Hematopoietic Defects
Cell Biology Research
- Signal Transduction
Mouse/Human Gene Homologs
- systemic lupus erythematosus
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
  - T cell deficiency
- Thymus Defects
  - B and T cell deficient

Genotype: Yaa related

Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - lupus erythematosus

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Il21r^tm1Wjl/Il21r^tm1Wjl X/Yaa
BXSB.129(Cg)-Il21r/Dcr

immune system phenotype

decreased susceptibility to systemic lupus erythematosus

mammalian phenotype

mortality/aging
- Normal - the hypergammaglobulinemia, autoantibody production, reduced frequencies of marginal zone B cells and monocytosis, renal disease, and premature morbidity that are found in Yaa bearing mice with at least one wildtype copy of the interleukin 21 receptor are ameliorated or prevented by the disruption of the interleukin 21 receptor
- Normal - ameliorated or prevented by the disruption of the interleukin 21 receptor
- Normal - unlike IL21R heterozygous B2M null controls, these double homozygotes do not develop the Lupus-like autoimmune syndrome caused by Yaa and generally survive beyond 40 weeks of age

References

Bubier JA; Sproule TJ; Foreman O; Spolski R; Shaffer DJ; Morse HC 3rd; Leonard WJ; Roopenian DC. 2009. A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice. Proc Natl Acad Sci U S A 106(5):1518-23PubMed: 19164519 MGI: J:144484
McPhee CG; Sproule TJ; Shin DM; Bubier JA; Schott WH; Steinbuck MP; Avenesyan L; Morse HC 3rd; Roopenian DC. 2011. MHC class I family proteins retard systemic lupus erythematosus autoimmunity and B cell lymphomagenesis. J Immunol 187(9):4695-704PubMed: 21964024 MGI: J:179430
Ozaki K; Spolski R; Feng CG; Qi CF; Cheng J; Sher A; Morse HC 3rd; Liu C; Schwartzberg PL; Leonard WJ. 2002. A critical role for IL-21 in regulating immunoglobulin production. Science 298(5598):1630-4PubMed: 12446913 MGI: J:80474

Additional - Il21r^tm1Wjl related

Additional - Yaa related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Il21ralternate3
- Standard PCR:Generic Neo
- Probe:Generic Neo
- Genotyping resources and troubleshooting
Breeding Considerations

To maintain the live colony, homozygous mice may be bred together. Homozygous animals of both sexes do not develop the spontaneous autoimmune phenotype observed for BXSB/MpJ inbred mice (Stock No. 000740). 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 BXSB.Yaa/Il21r-KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #021568 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 Il21r<tm1Wjl>

Related Products and Services

Frozen Mouse Embryo	BXSB.129(Cg)-Il21r<tm1Wjl>/DcrJ Frozen Embryos	$2595.00
Frozen Mouse Embryo	BXSB.129(Cg)-Il21r<tm1Wjl>/DcrJ Frozen Embryos	$2595.00
Frozen Mouse Embryo	BXSB.129(Cg)-Il21r<tm1Wjl>/DcrJ Frozen Embryos	$3373.50
Frozen Mouse Embryo	BXSB.129(Cg)-Il21r<tm1Wjl>/DcrJ Frozen Embryos	$3373.50

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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/Il21r-KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Yaa

Allele Symbol: Yaa

Il21rtm1Wjl

Allele Symbol: Il21rtm1Wjl

Disease Terms

Research Areas By Phenotype

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

Genotype: Yaa related

Mammalian Phenotype Terms by Genotype

Genotype: Il21rtm1Wjl/Il21rtm1Wjl X/YaaBXSB.129(Cg)-Il21r/Dcr

immune system phenotype

mammalian phenotype

References

Additional - Il21rtm1Wjl related

Additional - Yaa 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

Il21r^tm1Wjl

Allele Symbol: Il21r^tm1Wjl

Genotype: Il21r^tm1Wjl/Il21r^tm1Wjl X/Yaa
BXSB.129(Cg)-Il21r/Dcr

Additional - Il21r^tm1Wjl related