NOD.129(Cg)-Il21r^tm1Wjl/DcrMmjax

Stock number: 034163
Product name: NOD/Il21r-KO

Research areas: Cell Biology Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

NOD/Il21r-KO mice develop a greatly reduced incidence of type 1 diabetes. This strain may be useful for studying the role of IL21 in type I diabetes.

Detailed description

Il21r (interleukin 21 receptor) encodes a type I cytokine receptor for IL21 and is expressed on T, B and NK cells. It is involved in immunoglobulin production, B cell differentiation and Th17 differentiation. IL-21R knockout (KO) mice contain a neomycin cassette that replaces the signal peptide through the transmembrane domain resulting in a frameshift mutation. Mice homozygous for the mutation are viable and fertile. When the Il-21R KO allele is backcrossed on to the inbred strain NOD/ShiLtJ, a model for type 1 diabetes, homozygous mice exhibit reduced numbers of Th17 cells, fail to develop lymphocytic infiltration into the pancreas, and develop elevated glucose levels at a much lower percentage than NOD mice (5% compared to 60%). Populations of CD4+ and CD8+ T cells as well as cytokine production are not altered in homozygotes. This strain may be useful for studying the role of IL21 in type I diabetes.

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 NOD/ShiLtJ for for at least 13 generations (N13).  Sperm was cryopreserved at N13F13 in 2011.

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.