Phenotypes associated with this allele

• Allele Symbol: Aire^tm1Pltn
• Allele Name: targeted mutation 1, Leena Peltonen
• Allele ID: MGI:2182940
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Aire^tm1Pltn/Aire^tm1Pltn	B6.129S4-Aire^tm1Pltn	MGI:5008645
hm2	Aire^tm1Pltn/Aire^tm1Pltn	involves: 129S4/SvJae * C57BL/6	MGI:2182941
ht3	Aire^tm1Pltn/Aire^+	involves: 129S4/SvJae * C57BL/6	MGI:2654848

Genotype
MGI:5008645

hm1

• Allelic Composition: Aire^tm1Pltn/Aire^tm1Pltn
• Genetic Background: B6.129S4-Aire^tm1Pltn

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

immune system

immune system phenotype ( J:115076 )

N • male mice exhibit normal spleen morphology and size

N • sera does not recognize human APS I autoantigens

enlarged spleen ( J:115076 )

• in aged female mice

increased spleen weight ( J:115076 )

• in aged female mice

abnormal myelopoiesis ( J:115076 )

• mice exhibit increased proliferation at the early and late stages of myelogenesis and accelerated differentiation of monocytic precursors compared with wild-type mice

decreased follicular B cell number ( J:115076 )

increased B cell number ( J:115076 )

• 3 of 8 mice exhibit increased frequency of B220+ B cells in the thymus compared with wild-type mice

• aged mice exhibit increased B cell infiltrate in the liver and thymus compared with wild-type mice

increased monocyte cell number ( J:115076 )

• in the blood

abnormal metallophilic macrophage morphology ( J:115076 )

• increased in numbers in the marginal zone and blood

abnormal spleen marginal zone morphology ( J:115076 )

• 4 of 11 mice exhibit marginal zone hyperplasia compared with wild-type mice

increased marginal zone B cell number ( J:115076 )

liver inflammation ( J:115076 )

• B cell infiltration

neoplasm

increased B cell derived lymphoma incidence ( J:115076 )

• in the marginal zone

growth/size/body

decreased body weight ( J:115076 )

• in female mice at 15 to 24 months of age

• however, male mice have normal body weight

enlarged spleen ( J:115076 )

• in aged female mice

increased spleen weight ( J:115076 )

• in aged female mice

liver/biliary system

liver inflammation ( J:115076 )

• B cell infiltration

hematopoietic system

enlarged spleen ( J:115076 )

• in aged female mice

increased spleen weight ( J:115076 )

• in aged female mice

abnormal definitive hematopoiesis ( J:115076 )

• mice fail to exhibit age-dependent extramedullary hematopoiesis in the spleen unlike wild-type mice

• mice exhibit increased turnover of monocytic myeloid precursors in the bone marrow compared to in wild-type mice

abnormal myelopoiesis ( J:115076 )

• mice exhibit increased proliferation at the early and late stages of myelogenesis and accelerated differentiation of monocytic precursors compared with wild-type mice

decreased follicular B cell number ( J:115076 )

increased B cell number ( J:115076 )

• 3 of 8 mice exhibit increased frequency of B220+ B cells in the thymus compared with wild-type mice

• aged mice exhibit increased B cell infiltrate in the liver and thymus compared with wild-type mice

increased monocyte cell number ( J:115076 )

• in the blood

abnormal metallophilic macrophage morphology ( J:115076 )

• increased in numbers in the marginal zone and blood

abnormal spleen marginal zone morphology ( J:115076 )

• 4 of 11 mice exhibit marginal zone hyperplasia compared with wild-type mice

increased marginal zone B cell number ( J:115076 )

Genotype
MGI:2182941

hm2

• Allelic Composition: Aire^tm1Pltn/Aire^tm1Pltn
• Genetic Background: involves: 129S4/SvJae * C57BL/6

endocrine/exocrine glands

absent adrenal gland ( J:77873 )

• absence of the adrenal glands is seen with incomplete penetrance; however, the thyroid and pancreas are normal

thymus atrophy ( J:77873 )

• thymic atrophy is seen in 2 of 14 mutants

immune system

increased T cell proliferation ( J:77873 )

• immunization with hen egg lysozyme antigen results in a 4-5-fold increase in proliferating response of peripheral T cells, with mutants showing twice as many T cells in the lymph nodes than controls

thymus atrophy ( J:77873 )

• thymic atrophy is seen in 2 of 14 mutants

abnormal T cell morphology ( J:77873 )

• the TCR-Vbeta repertoire is altered in peripheral T cells

increased autoantibody level ( J:77873 )

• 73% of homozygous mice generated autoantibodies against at least one of the organs (liver, testis, pancreas and adrenal gland) tested and 40% of mice contain autoantibodies against two or more of the organs

liver inflammation ( J:77873 )

• 50% of mutants exhibit accumulation of lymphocytes in periportal regions

liver/biliary system

liver inflammation ( J:77873 )

• 50% of mutants exhibit accumulation of lymphocytes in periportal regions

reproductive system

infertility ( J:77873 )

• 85% of male or female mutants fail to produce any litters

hematopoietic system

increased T cell proliferation ( J:77873 )

• immunization with hen egg lysozyme antigen results in a 4-5-fold increase in proliferating response of peripheral T cells, with mutants showing twice as many T cells in the lymph nodes than controls

thymus atrophy ( J:77873 )

• thymic atrophy is seen in 2 of 14 mutants

abnormal T cell morphology ( J:77873 )

• the TCR-Vbeta repertoire is altered in peripheral T cells

cellular

increased T cell proliferation ( J:77873 )

• immunization with hen egg lysozyme antigen results in a 4-5-fold increase in proliferating response of peripheral T cells, with mutants showing twice as many T cells in the lymph nodes than controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autoimmune polyendocrine syndrome type 1		DOID:0050167	OMIM:240300	J:77873

Genotype
MGI:2654848

ht3

• Allelic Composition: Aire^tm1Pltn/Aire⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

reproductive system

reduced fertility ( J:77873 )

• crosses of heterozygous with heterozygous breeding sets exhibit a 44% reduction in fertility compared to controls