These autoimmune regulator knock-out mice may be useful in studies related autoimmune disease and tolerance induction.
Christophe Benoist, Joslin Diabetes Center
Genetic Background | Generation |
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N12F2
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Aire | autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy) |
Starting at:
$278.00 Domestic price for female 4-week |
556.00 Domestic price for breeder pair |
Mice homozygous for the targeted allele are viable, normal in size and at birth do not display any gross physical or behavioral abnormalities. While a transcript may be generated from the targeted locus, a functional protein is not translated. Homozygous mice display a phenotype consistent with a broad defect in immunological tolerance induction. By four weeks of age histological analysis reveals lymphocytic infiltrates in some organs. Infiltrates become more prevalent as the mouse ages. Serum autoantibodies are detected by 3-6 months. The thymic medullary epithelial cell (MEC) number is doubled. Similarly, a near doubling in the numbers of activated/memory CD44hiCD62Llo T lymphocytes is observed. A loss or reduction in expression occurs for a substantial number of genes in MECs, an observation consistent with the targeted gene's role as a transcriptional activator. The Donating Investigator reports that homozygotes are not fertile (most homozygous females are sterile due to ovarian autoimmunity, homozygous males can only breed for a short time and are subfertile). This mutant mouse strain may be useful in studies related autoimmune disease 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. 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 resulting chimeric animals were crossed to C57BL/6 mice. Heterozygous offspring were crossed to C57BL/6 for at least nine generations (October 2009).
A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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 43 markers, on Chromosome 12, was segregating with 129.
Allele Name | targeted mutation 1.1, Christophe Benoist and Diane Mathis |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Aire-; Aireo; HD Aire- |
Gene Symbol and Name | Aire, autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy) |
Gene Synonym(s) | |
Strain of Origin | 129S2/SvPas |
Chromosome | 10 |
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. The Donating Investigator reports that homozygotes are not fertile (most homozygous females are sterile due to ovarian autoimmunity, homozygous males can only breed for a short time and are subfertile).
When using the Aire- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004743 in your Materials and Methods section.
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wild-type for Aire<tm1.1Doi> |
Frozen Mouse Embryo | B6.129S2-Aire<tm1.1Doi>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129S2-Aire<tm1.1Doi>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129S2-Aire<tm1.1Doi>/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | B6.129S2-Aire<tm1.1Doi>/J Frozen Embryos | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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