Mouse Genome Informatics
hm1
     Airetm1Pltn/Airetm1Pltn
B6.129S4-Airetm1Pltn
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
immune system
immune system phenotype ( J:115076 )
N
• male mice exhibit normal spleen morphology and size (J:115076)
• sera does not recognize human APS I autoantigens (J:115076)
decreased splenocyte proliferation ( J:109554 )
• alpha-GalCer-induced
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
decreased NK T cell number ( J:109554 )
• mice exhibit fewer invariant NKT cells in the thymus, spleen, liver, and bone marrow compared with wild-type mice
abnormal metallophilic macrophage morphology ( J:115076 )
• increased in numbers in the marginal zone and blood
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
enlarged spleen ( J:115076 )
• in aged female mice
increased spleen weight ( J:115076 )
• in aged female mice
abnormal spleen marginal zone morphology ( J:115076 )
• 4 of 11 mice exhibit marginal zone hyperplasia compared with wild-type mice
abnormal thymus physiology ( J:109554 )
• alpha-GalCer-induced thymocyte proliferation is lower than in wild-type mice
abnormal NK T cell physiology ( J:109554 )
• mice exhibit impaired invariant NK T cell maturation compared with wild-type mice
decreased interleukin-2 secretion ( J:109554 )
• in CD45- cells induced with alpha-GalCer
decreased autoantibody level ( J:109554 )
• alpha-GalCer-induced
liver inflammation ( J:115076 )
• B cell infiltration

tumorigenesis
B cell derived lymphoma ( J:115076 )
• in the marginal zone

growth/size
decreased body weight ( J:115076 )
• in female mice at 15 to 24 months of age
• however, male mice have normal body weight

liver/biliary system
liver inflammation ( J:115076 )
• B cell infiltration

hematopoietic system
decreased splenocyte proliferation ( J:109554 )
• alpha-GalCer-induced
abnormal 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
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
decreased NK T cell number ( J:109554 )
• mice exhibit fewer invariant NKT cells in the thymus, spleen, liver, and bone marrow compared with wild-type mice
abnormal metallophilic macrophage morphology ( J:115076 )
• increased in numbers in the marginal zone and blood
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
enlarged spleen ( J:115076 )
• in aged female mice
increased spleen weight ( J:115076 )
• in aged female mice
abnormal spleen marginal zone morphology ( J:115076 )
• 4 of 11 mice exhibit marginal zone hyperplasia compared with wild-type mice
abnormal thymus physiology ( J:109554 )
• alpha-GalCer-induced thymocyte proliferation is lower than in wild-type mice

cellular
decreased splenocyte proliferation ( J:109554 )
• alpha-GalCer-induced


Mouse Genome Informatics
hm2
     Airetm1Pltn/Airetm1Pltn
involves: 129S4/SvJae * C57BL/6
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
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

immune system
abnormal T cell morphology ( J:77873 )
• the TCR-Vbeta repertoire is altered in peripheral T cells
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
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
abnormal T cell morphology ( J:77873 )
• the TCR-Vbeta repertoire is altered in peripheral T cells
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

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
 OMIM IDRef(s)
Autoimmune Polyendocrine Syndrome, Type I; APS1 240300 J:77873


Mouse Genome Informatics
hm3
     Airetm1Pltn/Airetm1Pltn
NOD.129S4-Airetm1Pltn
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
immune system
decreased NK T cell number ( J:109554 )
• mice exhibit fewer invariant NKT cells in the thymus, spleen, liver, and bone marrow compared with wild-type mice

hematopoietic system
decreased NK T cell number ( J:109554 )
• mice exhibit fewer invariant NKT cells in the thymus, spleen, liver, and bone marrow compared with wild-type mice


Mouse Genome Informatics
ht4
     Airetm1Pltn/Aire+
involves: 129S4/SvJae * C57BL/6
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
reproductive system
reduced fertility ( J:77873 )
• crosses of heterozygous with heterozygous breeding sets exhibit a 44% reduction in fertility compared to controls