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.
Dr. Derry Roopenian, The Jackson Laboratory
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Spontaneous | Yaa | accelerated autoimmunity and lymphoproliferation transposition |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Il21r | interleukin 21 receptor |
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.
The IL-21R null allele (Il21rtm1Wjl) 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).
Allele Name | accelerated autoimmunity and lymphoproliferation |
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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. |
Allele Name | targeted mutation 1, Warren J Leonard |
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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. |
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.
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Il21r<tm1Wjl> |
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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