Overview

This faculty strain has been discontinued but is available as Stock No. 021568.

The Yaa bearing BXSB/MpJ congenic males homozygous for the Il21r^tm1.1Hm null allele do not develop the spontaneous lupus-like autoimmune syndrome that normally develops in BXSB/MpJ males. This strain is valuable for the assessment of the role of IL21 signaling in this autoimmune disease and has been used to delineate the cell types and interactions essential for the development of this autoimmune disorder.

Genetic overview

Genetic Background	Generation
000740 BXSB/MpJ

Il21r^tm1Wjl

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

Yaa

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

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools

View All Research Applications

Details

Detailed Description

Due to the Yaa translocation on the Y Chromosome, BXSB/MpJ males (Stock No. 000740) develop a spontaneous lupus-like autoimmune syndrome. The first deaths occur at approximately 13 weeks of age with 50% lethality by approximately 30 weeks and 76% lethality by approximately 40 weeks. BXSB/MpJ females develop a greatly attenuated form of autoimmune disease because they lack Yaa. Bubier et al. (2009) determined that interleukin 21 signaling to B cells is essential for this autoimmune response and that BXSB/MpJ males homozygous for the Il21r^tm1.1Hm null allele do not develop the hypergammaglobulinemia, autoantibody production, or other autoimmune disease phentoypes that occur in BXSB/MpJ males and in BXSB/MpJ males heterozygous for the Il21r^tm1.1Hm null allele. Rather these homozygotes are viable and fertile with a lifespan usually exceeding 40 weeks of age. This strain is valuable for the assessment of the role of IL21 signaling in this autoimmune disease and has been used to delineate the cell types and interactions essential for the development of this autoimmune disorder (McPhee et al., 2013).

Development

The Il21r^tm1Wjl null allele was generated in a 129-derived ES cell and bred at least once to C57BL/6. This allele was subsequently backcrossed for 6 generations onto BALB/c before being bred to C57BL/6J for importation into The Jackson Laboratory by Dr. Derry Roopenian. This allele was then backcrossed onto BXSB/MpJ (Stock No. 000740) for 11 generations, retaining the Yaa-bearing Y Chromosome, and then sibling intercrossed to homozygosity for Il21r^tm1Wjl.

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

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Genetics

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.

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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Yaa related

Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - lupus erythematosus

Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
Research Tools
- Immunology, Inflammation and Autoimmunity Research

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 - ameliorated or prevented by the disruption of the interleukin 21 receptor
- 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 - 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

Additional - Il21r^tm1Wjl related

Additional - Yaa related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- 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
Mating System
- Homozygote x Homozygote

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

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Licensing Information

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Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Il21rtm1Wjl

Allele Symbol: Il21rtm1Wjl

Yaa

Allele Symbol: Yaa

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

Mating System

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Il21r^tm1Wjl

Allele Symbol: Il21r^tm1Wjl

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

Additional - Il21r^tm1Wjl related