B6.129-Il21r^tm1Kopf/J

Stock number: 019115
Product name: Il-21r^-
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

OVA or parasite challenge of these Il21r knockout mice developed by Dr. Manfred Kopf results in impaired Th2 type effector responses. This strain may be useful for studying IL21 in T and B cell response to various pathogens and in models of allergies and autoimmunity.

Detailed description

IL21R is a type I cytokine receptor for IL21. Type 1 cytokines are involved in T cell proliferation, differentiation, and maintenance of memory population. Ligand binding of IL21R activates downstream signaling through the JAK/STAT pathway.

In this strain, developed by Drs. Manfred Kopf and Martin Hodge, a neomycin cassette replaces exons 2-5 of the targeted allele, Il21r^tm1Kopf. Mice homozygous for the mutation are viable, fertile, and do not display any gross physical or behavioral abnormalities.

OVA airway challenge and infection with gastrointestinal nematodes of Il21r-/- mice resulted in impaired Th2 type effector responses (i.e. reduced numbers of IL-4 producing cells, basophils, eosinophils, and intestinal granuloma). In contrast, no differences were observed in development of Th17 cells and organ-related autoimmunity in models of experimental allergic encephalitis (EAE) and myocarditis (EAM). Further studies showed that Il21r-/- mice were highly susceptible to chronic viral infection due to a defect in maintenance of polyfunctional anti-viral CD8 T cell responses. This strain may be useful for studying the role of IL21 in T and B cell responses to various pathogens and in models of allergies and autoimmunity.

When referencing the use of this strain, please be sure to use this citation: Frohlich A. et al., Blood 2007 109(5):2023-31.

Development

A targeting vector was designed to exchange a neomycin selection cassette for exons 2 to 5 of the Il12r gene. The construct was electroporated into 129/Sv derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred to C57BL/6 mice. F1 progeny were crossed to C57BL/6NCrl for at least 4 generations (see SNP note below). Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One of the 27 markers throughout the genome was segregating suggested a C57BL/6 genetic background, as well as 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Allele

Symbol: Il21r^tm1Kopf
Name: targeted mutation 1, Manfred Kopf
MGI accession ID: MGI:3800291
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Il21r
Marker name: interleukin 21 receptor
Chromosome: 7
Strain of origin: 129/Sv
Molecular note: Exons 2 through 5 were replaced with a neo cassette. The absence of transcript was confirmed by RT-PCR on splenocyte extracts.