Phenotypes associated with this allele

• Allele Symbol: Aire^tm1Ptsn
• Allele Name: targeted mutation 1, Part Peterson
• Allele ID: MGI:3722595
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Aire^tm1Ptsn/Aire^tm1Ptsn	C57BL/6-Aire^tm1Ptsn	MGI:3836627
hm2	Aire^tm1Ptsn/Aire^tm1Ptsn	C.B6-Aire^tm1Ptsn	MGI:5140806

Genotype
MGI:3836627

hm1

• Allelic Composition: Aire^tm1Ptsn/Aire^tm1Ptsn
• Genetic Background: C57BL/6-Aire^tm1Ptsn

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

immune system

parotid gland inflammation ( J:145910 )

• 80% of mice have severe inflammation of the parotid gland

sublingual gland inflammation ( J:145910 )

• 40% of mce have severe inflammation of the sublingual gland

abnormal thymus medulla morphology ( J:145910 )

• mice have 4-fold more MHC-II^high medullary thymic epithelial cells than controls

• the immature medullary thymic epithelial compartment is reduced by 4-fold

abnormal T cell activation ( J:145910 )

• there is 5% increase in activated CD69^high CD4⁺ T cells in lymph nodes but not spleen

• there is also an increase in CD44^high CD4 T cells in the spleen and lymph nodes

increased autoantibody level ( J:145910 )

• all mice examined have antibodies against pancreas and liver antigens

• 75% of mice have antibodies against testis, lung, salivary gland, and eye antigens

vitreous body inflammation ( J:145910 )

• vitritis is noted in some mice

uveitis ( J:145910 )

• mice develop an autoimmune uveitis with 40% of mice developing severe retinal damage and the majority of mice displaying a distortion of the outer and inner nuclear layer

reproductive system

reduced male fertility ( J:145910 )

♂ • there is a 73% fertilization success rate with mutant sperm compared to 93% for wild-type sperm

endocrine/exocrine glands

parotid gland inflammation ( J:145910 )

• 80% of mice have severe inflammation of the parotid gland

sublingual gland inflammation ( J:145910 )

• 40% of mce have severe inflammation of the sublingual gland

abnormal thymus medulla morphology ( J:145910 )

• mice have 4-fold more MHC-II^high medullary thymic epithelial cells than controls

• the immature medullary thymic epithelial compartment is reduced by 4-fold

vision/eye

vitreous body inflammation ( J:145910 )

• vitritis is noted in some mice

uveitis ( J:145910 )

• mice develop an autoimmune uveitis with 40% of mice developing severe retinal damage and the majority of mice displaying a distortion of the outer and inner nuclear layer

hematopoietic system

abnormal thymus medulla morphology ( J:145910 )

• mice have 4-fold more MHC-II^high medullary thymic epithelial cells than controls

• the immature medullary thymic epithelial compartment is reduced by 4-fold

abnormal T cell activation ( J:145910 )

• there is 5% increase in activated CD69^high CD4⁺ T cells in lymph nodes but not spleen

• there is also an increase in CD44^high CD4 T cells in the spleen and lymph nodes

digestive/alimentary system

parotid gland inflammation ( J:145910 )

• 80% of mice have severe inflammation of the parotid gland

sublingual gland inflammation ( J:145910 )

• 40% of mce have severe inflammation of the sublingual gland

Genotype
MGI:5140806

hm2

• Allelic Composition: Aire^tm1Ptsn/Aire^tm1Ptsn
• Genetic Background: C.B6-Aire^tm1Ptsn

immune system

stomach inflammation ( J:174653 )

• mutants exhibit immune cell infiltrates into the gastric mucosa at around 28-35 weeks of age, indicating development of autoimmune gastritis at this age

abnormal cytokine level ( J:174653 )

• mutants exhibit higher levels of IL-12, IL-23, TNF-alpha, and IL-6 in the stomachs during mucosal candidiasis, particularly at 2 weeks after infection, at a time when production of these cytokines declines in wild-type mice, indicating an excessive inflammatory response in mutants

abnormal adaptive immunity ( J:174653 )

• one week after fungal infection, mutants show a reduced fungal growth in the stomachs, suggesting that the adaptive, more than the innate, immune response is dysfunctional, however 2 weeks after infection, mutants show increased susceptibility to mucosal candidiasis

abnormal T-helper 1 physiology ( J:174653 )

• mutants exhibit an increase in C. albicans induced Th1-cell responses

abnormal T-helper 17 cell physiology ( J:174653 )

• mutants exhibit an increase in C. albicans induced Th17-cell responses

abnormal regulatory T cell physiology ( J:174653 )

• mutants exhibit decreased Treg responses to C. albicans infection

increased interleukin-12 secretion ( J:174653 )

• mutants exhibit higher levels of IL-12 in the stomachs during mucosal candidiasis

increased interleukin-23 secretion ( J:174653 )

• mutants exhibit higher levels of IL-23 in the stomachs during mucosal candidiasis

increased interleukin-6 secretion ( J:174653 )

• mutants exhibit higher levels of IL-6 in the stomachs during mucosal candidiasis

increased tumor necrosis factor secretion ( J:174653 )

• mutants exhibit higher levels of TNF-alpha in the stomachs during mucosal candidiasis

increased susceptibility to autoimmune disorder ( J:174653 )

• older mutants (28-35 weeks) develop autoimmune gastritis

decreased susceptibility to fungal infection ( J:174653 )

• naive mutants are more resistant than wild-type mice to primary disseminated infection with the fungus, as indicated by increased survival upon systemic, disseminated infection

increased susceptibility to fungal infection ( J:174653 )

• mutants exhibit increased susceptibility to mucosal candidiasis, as indicated by an inability to clear the fungus from the stomach and colon two weeks after infection and by dissemination to the liver

• however, one week after fungal infection, mutants show a reduced fungal growth in the stomachs, suggesting that the adaptive, more than the innate, immune response is dysfunctional

• mutants with mucosal candidiasis do not exhibit resistance to systemic re-infection as seen in wild-type mice, suggesting that protective memory responses to the fungus are impaired in mutant

digestive/alimentary system

stomach inflammation ( J:174653 )

• mutants exhibit immune cell infiltrates into the gastric mucosa at around 28-35 weeks of age, indicating development of autoimmune gastritis at this age

homeostasis/metabolism

abnormal cytokine level ( J:174653 )

• mutants exhibit higher levels of IL-12, IL-23, TNF-alpha, and IL-6 in the stomachs during mucosal candidiasis, particularly at 2 weeks after infection, at a time when production of these cytokines declines in wild-type mice, indicating an excessive inflammatory response in mutants

hematopoietic system

abnormal T-helper 1 physiology ( J:174653 )

• mutants exhibit an increase in C. albicans induced Th1-cell responses

abnormal T-helper 17 cell physiology ( J:174653 )

• mutants exhibit an increase in C. albicans induced Th17-cell responses

abnormal regulatory T cell physiology ( J:174653 )

• mutants exhibit decreased Treg responses to C. albicans infection