Autoimmune regulator knockout mice may be useful in studies related autoimmune disease and tolerance induction.
Christophe Benoist, Joslin Diabetes Center
Autoimmune regulator, Aire, located on Chromosome 10, 41.6cm controls, in part, ectopic gene expression involved with tolerance induction, and is specifically involved with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in humans. Exon 2 and portions of the flanking introns of the Aire gene were deleted by Cre-lox-mediated homologous recombination. Analysis of the mutated Aire transcript identified a frameshift that precludes translation past exon 1. The Aire mutation originated on a 129B6F2 background and was backcrossed to NOD for 12 generations. NOD.Aire deficient mice are normoglycemic, but experience weight loss between 5 and 15 weeks of age. Approximately 79% die spontaneously or must be euthanized due to declining health at between 6 and 14 weeks of age. Pathology indicates lung lesions with generalized pneumonitis, severe exocrine (not endocrine) pancreatitis and lymphocytic infiltration in the liver, salivary, stomach, reproductive systems, and the presence of circulating autoantibodies against ovary, stomach, retina and exocrine pancreas.
This stock is useful in the study of Aire function in autoimmunity and tolerance induction.
To create this mutant the originating investigator employed a targeting vector bearing a loxP site-flanked Pgk-neo cassette inserted into intron 2. An additional single loxP site was placed in intron 1. The targeting construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells, and correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric mice were mated with CMV-cre transgenic mice on a C57BL/6 background. Exon 2 and portions of introns 1 and 3 were excised in the offspring. The C57BL/6 Aire deficient stock was then backcrossed to NOD for 12 generations. In 2007, the T1DR received this strain at generation N12F5.
|Allele Name||targeted mutation 1.1, Christophe Benoist and Diane Mathis|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Aire-; Aireo; HD Aire-|
|Gene Symbol and Name||Aire, autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)|
|Strain of Origin||129S2/SvPas|
|Molecular Note||The floxed fragment containing exon 2, portions of the surrounding introns, and a neo cassette were excised via cre mediated recombination in vivo. While shortened transcript was detected by RT-PCR analysis of homozygous mutant thymii, sequence analysis of the transcript identified a frameshift mutation resulting from the splicing of exons 1 and 3 that precludes translation past exon 1.|
|Mutations Made By|| |
Diane Mathis, Harvard Medical School
When maintaining a live colony, these mice can be bred as heterozygotes. Approximately 79% of homozygotes die spontaneously or must be euthanized due to declining health at between 6 and 14 weeks of age.
When using the NOD.Aire KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006360 in your Materials and Methods section.