BXSB.129(Cg)-Il21r^tm1Wjl/Dcr

Stock number: 005985
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

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.

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.

Allele

Symbol: Il21r^tm1Wjl
Name: targeted mutation 1, Warren J Leonard
MGI accession ID: MGI:2446509
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: IL-21R^-
Marker symbol: Il21r
Marker name: interleukin 21 receptor
Marker synonyms: CD360; IMD56; NILR
Chromosome: 7
Strain of origin: 129
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.

Allele

Symbol: Yaa
Name: accelerated autoimmunity and lymphoproliferation
MGI accession ID: MGI:1856277
Generation method: Spontaneous
Synonyms: Is(XOfd1-Mid1;Y)1Mp; Tp(X;Y)1Ekw
Marker symbol: Yaa
Marker name: accelerated autoimmunity and lymphoproliferation transposition
Marker synonyms: Tp(X;Y)1Ekw
Chromosome: Y
Strain of origin: SB/Le
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.