Strain Name:

B6.129S2-Airetm1.1Doi/J

Stock Number:

004743

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Availability:

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These autoimmune regulator knock-out mice may be useful in studies related autoimmune disease and tolerance induction.

Description

Strain Information

Type Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHeterozygote x Heterozygote         (Female x Male)   01-MAR-06
Specieslaboratory mouse
GenerationN10F9 (28-DEC-13)
Generation Definitions
 
Donating Investigator Christophe Benoist,   Joslin Diabetes Center

Description
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.

Development
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).

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Airetm1.1Doi allele
006360   NOD.129S2(B6)-Airetm1.1Doi/DoiJ
View Strains carrying   Airetm1.1Doi     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Autoimmune Polyendocrine Syndrome, Type I, with or without Reversible Metaphyseal Dysplasia; APS1
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Airetm1.1Doi/Airetm1.1Doi

        involves: 129S2/SvPas * C57BL/6
  • immune system phenotype
  • abnormal thymus medulla morphology
    • thymic medullary cell (MEC) number is doubled   (MGI Ref ID J:83422)
  • increased T cell number
    • near doubling of the number of activated/memory CD44hiCD62Llo T cells   (MGI Ref ID J:83422)
  • increased autoantibody level
    • autoantibodies develop against the stomach   (MGI Ref ID J:119475)
  • increased susceptibility to autoimmune disorder
    • lymphatic infiltrates in specific regions of multiple organs   (MGI Ref ID J:83422)
    • infiltration is progressive with age   (MGI Ref ID J:83422)
  • stomach inflammation
    • chronic inflammation of the stomach, particularly of the stomach mucosa   (MGI Ref ID J:119475)
  • hematopoietic system phenotype
  • abnormal thymus medulla morphology
    • thymic medullary cell (MEC) number is doubled   (MGI Ref ID J:83422)
  • increased T cell number
    • near doubling of the number of activated/memory CD44hiCD62Llo T cells   (MGI Ref ID J:83422)
  • digestive/alimentary phenotype
  • stomach inflammation
    • chronic inflammation of the stomach, particularly of the stomach mucosa   (MGI Ref ID J:119475)
  • endocrine/exocrine gland phenotype
  • abnormal thymus medulla morphology
    • thymic medullary cell (MEC) number is doubled   (MGI Ref ID J:83422)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Airetm1.1Doi
Allele Name targeted mutation 1.1, Christophe Benoist and Diane Mathis
Allele Type Targeted (Null/Knockout)
Common Name(s) Aire-; Aireo; HD Aire-;
Mutation Made By Diane Mathis,   Harvard Medical School
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Aire, autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)
Chromosome 10
Gene Common Name(s) AIRE1; APECED; APS1; APSI; PGA1;
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. [MGI Ref ID J:83422]

Genotyping

Genotyping Information

Genotyping Protocols

Airetm1.1Doi,

SEPARATED MELT



Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Anderson MS; Venanzi ES; Klein L; Chen Z; Berzins SP; Turley SJ; von Boehmer H; Bronson R; Dierich A; Benoist C; Mathis D. 2002. Projection of an immunological self shadow within the thymus by the aire protein. Science 298(5597):1395-401. [PubMed: 12376594]  [MGI Ref ID J:83422]

Additional References

Airetm1.1Doi related

Anderson MS; Venanzi ES; Chen Z; Berzins SP; Benoist C; Mathis D. 2005. The cellular mechanism of Aire control of T cell tolerance. Immunity 23(2):227-39. [PubMed: 16111640]  [MGI Ref ID J:100515]

Chen J; Qian H; Horai R; Chan CC; Falick Y; Caspi RR. 2013. Comparative analysis of induced vs. spontaneous models of autoimmune uveitis targeting the interphotoreceptor retinoid binding protein. PLoS One 8(8):e72161. [PubMed: 24015215]  [MGI Ref ID J:206410]

Chen YF; Zhou D; Metzger T; Gallup M; Jeanne M; Gould DB; Anderson MS; McNamara NA. 2014. Spontaneous development of autoimmune uveitis Is CCR2 dependent. Am J Pathol 184(6):1695-705. [PubMed: 24736166]  [MGI Ref ID J:211671]

Chen YT; Chen FY; Vijmasi T; Stephens DN; Gallup M; McNamara NA. 2013. Pax6 downregulation mediates abnormal lineage commitment of the ocular surface epithelium in aqueous-deficient dry eye disease. PLoS One 8(10):e77286. [PubMed: 24143217]  [MGI Ref ID J:209118]

Chen YT; Lazarev S; Bahrami AF; Noble LB; Chen FY; Zhou D; Gallup M; Yadav M; McNamara NA. 2012. Interleukin-1 receptor mediates the interplay between CD4(+) T cells and ocular resident cells to promote keratinizing squamous metaplasia in Sjogren's syndrome. Lab Invest 92(4):556-70. [PubMed: 22231738]  [MGI Ref ID J:181948]

Chen YT; Nikulina K; Lazarev S; Bahrami AF; Noble LB; Gallup M; McNamara NA. 2010. Interleukin-1 as a phenotypic immunomodulator in keratinizing squamous metaplasia of the ocular surface in Sjogren's syndrome. Am J Pathol 177(3):1333-43. [PubMed: 20696775]  [MGI Ref ID J:163691]

Chen Z; Benoist C; Mathis D. 2005. How defects in central tolerance impinge on a deficiency in regulatory T cells. Proc Natl Acad Sci U S A 102(41):14735-40. [PubMed: 16203996]  [MGI Ref ID J:102496]

Danso-Abeam D; Staats KA; Franckaert D; Van Den Bosch L; Liston A; Gray DH; Dooley J. 2013. Aire mediates thymic expression and tolerance of pancreatic antigens via an unconventional transcriptional mechanism. Eur J Immunol 43(1):75-84. [PubMed: 23041971]  [MGI Ref ID J:191104]

DeVoss J; Hou Y; Johannes K; Lu W; Liou GI; Rinn J; Chang H; Caspi RR; Fong L; Anderson MS. 2006. Spontaneous autoimmunity prevented by thymic expression of a single self-antigen. J Exp Med 203(12):2727-35. [PubMed: 17116738]  [MGI Ref ID J:124583]

DeVoss JJ; LeClair NP; Hou Y; Grewal NK; Johannes KP; Lu W; Yang T; Meagher C; Fong L; Strauss EC; Anderson MS. 2010. An autoimmune response to odorant binding protein 1a is associated with dry eye in the aire-deficient mouse. J Immunol 184(8):4236-46. [PubMed: 20237294]  [MGI Ref ID J:159869]

Devoss JJ; Shum AK; Johannes KP; Lu W; Krawisz AK; Wang P; Yang T; Leclair NP; Austin C; Strauss EC; Anderson MS. 2008. Effector mechanisms of the autoimmune syndrome in the murine model of autoimmune polyglandular syndrome type 1. J Immunol 181(6):4072-9. [PubMed: 18768863]  [MGI Ref ID J:139094]

Dooley J; Erickson M; Farr AG. 2008. Alterations of the medullary epithelial compartment in the Aire-deficient thymus: implications for programs of thymic epithelial differentiation. J Immunol 181(8):5225-32. [PubMed: 18832676]  [MGI Ref ID J:140094]

Gavanescu I; Benoist C; Mathis D. 2008. B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients. Proc Natl Acad Sci U S A 105(35):13009-14. [PubMed: 18755889]  [MGI Ref ID J:139126]

Gavanescu I; Kessler B; Ploegh H; Benoist C; Mathis D. 2007. Loss of Aire-dependent thymic expression of a peripheral tissue antigen renders it a target of autoimmunity. Proc Natl Acad Sci U S A 104(11):4583-7. [PubMed: 17360567]  [MGI Ref ID J:119475]

Gillard GO; Dooley J; Erickson M; Peltonen L; Farr AG. 2007. Aire-dependent alterations in medullary thymic epithelium indicate a role for Aire in thymic epithelial differentiation. J Immunol 178(5):3007-15. [PubMed: 17312146]  [MGI Ref ID J:144101]

Giraud M; Yoshida H; Abramson J; Rahl PB; Young RA; Mathis D; Benoist C. 2012. Aire unleashes stalled RNA polymerase to induce ectopic gene expression in thymic epithelial cells. Proc Natl Acad Sci U S A 109(2):535-40. [PubMed: 22203960]  [MGI Ref ID J:179981]

Gray D; Abramson J; Benoist C; Mathis D. 2007. Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J Exp Med 204(11):2521-8. [PubMed: 17908938]  [MGI Ref ID J:126040]

Gray DH; Gavanescu I; Benoist C; Mathis D. 2007. Danger-free autoimmune disease in Aire-deficient mice. Proc Natl Acad Sci U S A 104(46):18193-8. [PubMed: 17991771]  [MGI Ref ID J:127308]

Guerau-de-Arellano M; Martinic M; Benoist C; Mathis D. 2009. Neonatal tolerance revisited: a perinatal window for Aire control of autoimmunity. J Exp Med 206(6):1245-52. [PubMed: 19487417]  [MGI Ref ID J:149510]

He Q; Morillon YM 2nd; Spidale NA; Kroger CJ; Liu B; Sartor RB; Wang B; Tisch R. 2013. Thymic development of autoreactive T cells in NOD mice is regulated in an age-dependent manner. J Immunol 191(12):5858-66. [PubMed: 24198282]  [MGI Ref ID J:207147]

Hou Y; DeVoss J; Dao V; Kwek S; Simko JP; McNeel DG; Anderson MS; Fong L. 2009. An aberrant prostate antigen-specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans. J Clin Invest 119(7):2031-41. [PubMed: 19603556]  [MGI Ref ID J:152543]

Jasti S; Warren BD; McGinnis LK; Kinsey WH; Petroff BK; Petroff MG. 2012. The autoimmune regulator prevents premature reproductive senescence in female mice. Biol Reprod 86(4):110. [PubMed: 22219212]  [MGI Ref ID J:185765]

Jiang W; Anderson MS; Bronson R; Mathis D; Benoist C. 2005. Modifier loci condition autoimmunity provoked by Aire deficiency. J Exp Med 202(6):805-15. [PubMed: 16172259]  [MGI Ref ID J:107432]

Koh AS; Kingston RE; Benoist C; Mathis D. 2010. Global relevance of Aire binding to hypomethylated lysine-4 of histone-3. Proc Natl Acad Sci U S A 107(29):13016-21. [PubMed: 20615959]  [MGI Ref ID J:162311]

Li S; Nikulina K; DeVoss J; Wu AJ; Strauss EC; Anderson MS; McNamara NA. 2008. Small proline-rich protein 1B (SPRR1B) is a biomarker for squamous metaplasia in dry eye disease. Invest Ophthalmol Vis Sci 49(1):34-41. [PubMed: 18172072]  [MGI Ref ID J:132504]

Misharin AV; Nagayama Y; Aliesky HA; Rapoport B; McLachlan SM. 2009. Studies in mice deficient for the autoimmune regulator (Aire) and transgenic for the thyrotropin receptor reveal a role for Aire in tolerance for thyroid autoantigens. Endocrinology 150(6):2948-56. [PubMed: 19264867]  [MGI Ref ID J:158187]

Schaller CE; Wang CL; Beck-Engeser G; Goss L; Scott HS; Anderson MS; Wabl M. 2008. Expression of Aire and the early wave of apoptosis in spermatogenesis. J Immunol 180(3):1338-43. [PubMed: 18209027]  [MGI Ref ID J:131354]

Shum AK; DeVoss J; Tan CL; Hou Y; Johannes K; O'Gorman CS; Jones KD; Sochett EB; Fong L; Anderson MS. 2009. Identification of an autoantigen demonstrates a link between interstitial lung disease and a defect in central tolerance. Sci Transl Med 1(9):9ra20. [PubMed: 20368189]  [MGI Ref ID J:167884]

Su MA; Giang K; Zumer K; Jiang H; Oven I; Rinn JL; Devoss JJ; Johannes KP; Lu W; Gardner J; Chang A; Bubulya P; Chang HY; Peterlin BM; Anderson MS. 2008. Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in Aire. J Clin Invest 118(5):1712-26. [PubMed: 18414681]  [MGI Ref ID J:135154]

Taniguchi RT; Devoss JJ; Moon JJ; Sidney J; Sette A; Jenkins MK; Anderson MS. 2012. Detection of an autoreactive T-cell population within the polyclonal repertoire that undergoes distinct autoimmune regulator (Aire)-mediated selection. Proc Natl Acad Sci U S A 109(20):7847-52. [PubMed: 22552229]  [MGI Ref ID J:184783]

Venanzi ES; Gray DH; Benoist C; Mathis D. 2007. Lymphotoxin pathway and Aire influences on thymic medullary epithelial cells are unconnected. J Immunol 179(9):5693-700. [PubMed: 17947641]  [MGI Ref ID J:153012]

Venanzi ES; Melamed R; Mathis D; Benoist C. 2008. The variable immunological self: genetic variation and nongenetic noise in Aire-regulated transcription. Proc Natl Acad Sci U S A 105(41):15860-5. [PubMed: 18838677]  [MGI Ref ID J:141423]

Vijmasi T; Chen FY; Chen YT; Gallup M; McNamara N. 2013. Topical administration of interleukin-1 receptor antagonist as a therapy for aqueous-deficient dry eye in autoimmune disease. Mol Vis 19:1957-65. [PubMed: 24068863]  [MGI Ref ID J:205292]

Yang S; Bansal K; Lopes J; Benoist C; Mathis D. 2013. Aire's plant homeodomain(PHD)-2 is critical for induction of immunological tolerance. Proc Natl Acad Sci U S A 110(5):1833-8. [PubMed: 23319629]  [MGI Ref ID J:193695]

Zhang X; Liu JQ; Shi Y; Reid HH; Boyd RL; Khattabi M; El-Omrani HY; Zheng P; Liu Y; Bai XF. 2012. CD24 on thymic APCs regulates negative selection of myelin antigen-specific T lymphocytes. Eur J Immunol 42(4):924-35. [PubMed: 22213356]  [MGI Ref ID J:187788]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen 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).
Mating SystemHeterozygote x Heterozygote         (Female x Male)   01-MAR-06
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $239.00Female or MaleHeterozygous for Airetm1.1Doi  
$239.00Female or MaleHomozygous for Airetm1.1Doi  
Price per Pair (US dollars $)Pair Genotype
$478.00Heterozygous for Airetm1.1Doi x Heterozygous for Airetm1.1Doi  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $310.70Female or MaleHeterozygous for Airetm1.1Doi  
$310.70Female or MaleHomozygous for Airetm1.1Doi  
Price per Pair (US dollars $)Pair Genotype
$621.40Heterozygous for Airetm1.1Doi x Heterozygous for Airetm1.1Doi  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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