These Irak3 knock out mice on the NOD background develop spontaneous Type I diabetes mellitus with an onset as early as 6 of 7 weeks of age.
Dr. Richard A. Flavell, Yale University School of Medicine
Li Wen, Yale School of Medicine
Mice that are homozygous for the targeted mutation are viable and fertile. On the NOD background, female homozygotes develop spontaneous Type I diabetes mellitus with an onset as early as 6 of 7 weeks of age. Male homozygotes on the NOD background also show a tendency for earlier onset of diabetes. Circulating anti-insulin antibody levels are elevated, more pancreatic islets are infiltrated, there is a higher proportion of effector/memory
cells, and an increase in CD4+ T cells in pancreatic draining lymph nodes, in female homozygotes, when compared to controls.
The targeting vector was designed to replace a 1.2 kb region of the gene (containing three exons encoding two-thirds of the kinase domain) with a loxP-flanked neomycin resistance cassette. The targeting vector was linearized and electroporated into 129S1/Sv-derived W9.5 embryonic stem (ES) cells. Targeted clones were injected into C57BL/6 blastocysts and resulting chimeric males were bred to C57BL/6 females. Interbreeding of heterozygotes was performed to generate homozygotes. This line was backcrossed to C57BL/6 for approximately 6 generations by the originating laboratory. The mice were obtained by Dr. Li Wen and backcrossed to NOD/Caj (Yale University) for 11 generations, and then intercrossed for 8 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to NOD/ShiLtJ (Stock No. 001976) at least once to establish the colony.
|Allele Name||targeted mutation 1, Richard A Flavell|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Irak3, interleukin-1 receptor-associated kinase 3|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||1.2 kb of sequence were replaced with a floxed neo cassette. The deleted region contained 3 exons encoding two thirds of the kinase domain. While Western blot analysis of LPS-stimulated bone marrow macrophage extracts using a carboxy terminal antibody confirmed the absence of normal protein in homozygous mutant mice, truncated transcript was detected by Northern blot analysis using an amino terminal probe. Sequence analysis of RT-PCR products revealed an in frame stop codon generated by aberrant splicing of the endogenous gene and the neo transgene.|
|Mutations Made By|| |
Dr. Richard Flavell, Yale University School of Medicine
When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to NOD/ShiLtJ inbred mice (Stock No. 001976). Female homozygotes develop spontaneous Type I diabetes mellitus with an onset as early as 6 of 7 weeks of age.
When using the IRAK-M-/-NOD mouse strain in a publication, please cite the originating article(s) and include JAX stock #022836 in your Materials and Methods section.