Mouse Genome Informatics
hm1
    Airetm1.1Doi/Airetm1.1Doi
(B6.129S2-Airetm1.1Doi x NOD.129S2(B6)-Airetm1.1Doi)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
N
• Background Sensitivity: both the pancreatitis and gastritis associated with Airetm1.1Doi homozygotes on the NOD background are absent in this F1 cross to C57BL/6 (J:107432)


Mouse Genome Informatics
hm2
    Airetm1.1Doi/Airetm1.1Doi
B6.129S2-Airetm1.1Doi/Doi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• Background Sensitivity: sialitis is observed in 20% of mice by 20 weeks of age which is a lower incidence than what is observed when the mutant allele is on the NOD or SJL backgrounds
• Background Sensitivity: gastritis occurs in only 9% of mice by 20 weeks of age on this background but has a much higher incidence when the mutant allele is on other backgrounds (100% in SJL and BALB/c, 87% in NOD)
• Background Sensitivity: mice generate autoantibodies with a reactivity that mirror the histopathology associated with this mouse strain
• Background Sensitivity: autoantibodies from these mice show only sporadic and weak reactivity to salivary and gastric antigens
• cornea inflammation occurs in 60% of mice by 20 weeks of age
• Background Sensitivity: lung inflammation is observed in 36% of mice by 20 weeks of age which is a much lower incidence than what is observed when the mutant allele is on other backgrounds

vision/eye
• cornea inflammation occurs in 60% of mice by 20 weeks of age
• Background Sensitivity: retinal degeneration resulting from autoimmune disease occurs by 20 weeks of age in 67% of mice

endocrine/exocrine glands
• Background Sensitivity: sialitis is observed in 20% of mice by 20 weeks of age which is a lower incidence than what is observed when the mutant allele is on the NOD or SJL backgrounds

digestive/alimentary system
• Background Sensitivity: sialitis is observed in 20% of mice by 20 weeks of age which is a lower incidence than what is observed when the mutant allele is on the NOD or SJL backgrounds
• Background Sensitivity: gastritis occurs in only 9% of mice by 20 weeks of age on this background but has a much higher incidence when the mutant allele is on other backgrounds (100% in SJL and BALB/c, 87% in NOD)

respiratory system
• Background Sensitivity: lung inflammation is observed in 36% of mice by 20 weeks of age which is a much lower incidence than what is observed when the mutant allele is on other backgrounds


Mouse Genome Informatics
hm3
    Airetm1.1Doi/Airetm1.1Doi
C.129S2-Airetm1.1Doi/Doi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• sialitis is observed in 20% of mice by 20 weeks of age which is a much lower incidence than what is observed when the mutant allele is on other backgrounds
• gastritis occurs in all mice by 20 weeks of age but is rarely observed in when the mutant allele is on the C57BL/6 background
• all mice have inflammation of the prostate by 20 weeks of age (J:107432)
• Background Sensitivity: mice generate autoantibodies with a reactivity that mirror the histopathology associated with this mouse strain
• Background Sensitivity: the autoantibodies from this strain consistently target stomach antigens with reactivity patterns distinctly different from the autoantibodies generated on the NOD background
• Background Sensitivity: cornea inflammation occurs in 60% of mice of this background by 20 weeks of age but is not observed when the mutant allele is on SJL or C57BL/6 background
• Background Sensitivity: liver inflammation is observed in 40% of mice by 20 weeks of age while no inflammation is present when the mutant allele is on the C57BL/6 background
• Background Sensitivity: all mice exhibit inflammation of the ovaries on this background but while no inflammation is observed in C57BL/6 mice carrying the mutant allele (J:107432)
• Background Sensitivity: lung inflammation is observed in 50% of mice by 20 weeks of age which is a much lower incidence than observed when the mutant allele is on the NOD or SJL backgrounds

vision/eye
• Background Sensitivity: cornea inflammation occurs in 60% of mice of this background by 20 weeks of age but is not observed when the mutant allele is on SJL or C57BL/6 background
• retinal degeneration resulting from autoimmune disease occurs by 20 weeks of age in 93% of mice

endocrine/exocrine glands
• sialitis is observed in 20% of mice by 20 weeks of age which is a much lower incidence than what is observed when the mutant allele is on other backgrounds
• all mice have inflammation of the prostate by 20 weeks of age (J:107432)

digestive/alimentary system
• sialitis is observed in 20% of mice by 20 weeks of age which is a much lower incidence than what is observed when the mutant allele is on other backgrounds
• gastritis occurs in all mice by 20 weeks of age but is rarely observed in when the mutant allele is on the C57BL/6 background

liver/biliary system
• Background Sensitivity: liver inflammation is observed in 40% of mice by 20 weeks of age while no inflammation is present when the mutant allele is on the C57BL/6 background

reproductive system
• all mice have inflammation of the prostate by 20 weeks of age (J:107432)
• Background Sensitivity: all mice exhibit inflammation of the ovaries on this background but while no inflammation is observed in C57BL/6 mice carrying the mutant allele (J:107432)

respiratory system
• Background Sensitivity: lung inflammation is observed in 50% of mice by 20 weeks of age which is a much lower incidence than observed when the mutant allele is on the NOD or SJL backgrounds


Mouse Genome Informatics
hm4
    Airetm1.1Doi/Airetm1.1Doi
involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Stomach autoimmunity in Airetm1.1Doi/Airetm1.1Doi mice

immune system
• chronic inflammation of the stomach, particularly of the stomach mucosa
• near doubling of the number of activated/memory CD44hiCD62Llo T cells
• thymic medullary cell (MEC) number is doubled
• lymphatic infiltrates in specific regions of multiple organs
• infiltration is progressive with age
• autoantibodies develop against the stomach

hematopoietic system
• near doubling of the number of activated/memory CD44hiCD62Llo T cells
• thymic medullary cell (MEC) number is doubled

digestive/alimentary system
• chronic inflammation of the stomach, particularly of the stomach mucosa


Mouse Genome Informatics
hm5
    Airetm1.1Doi/Airetm1.1Doi
involves: 129S2/SvPas * C57BL/6 * NOD
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• Background Sensitivity: a minor fraction of the mice from this F2 cross have gastritis
• Background Sensitivity: there is no correlation between pancreatitis and gastritis
• Background Sensitivity: a minor fraction of the mice from this F2 cross have pancreatitis
• Background Sensitivity: there is no correlation between pancreatitis and gastritis
• Background Sensitivity: a minor fraction of the mice from this F2 cross have inflammatory lesions in the liver
• Background Sensitivity: there some correlation between lung lesions and liver lesions
• Background Sensitivity: a minor fraction of the mice from this F2 cross have inflammatory lesions in the lung
• Background Sensitivity: there some correlation between lung lesions and liver lesions

endocrine/exocrine glands
• Background Sensitivity: a minor fraction of the mice from this F2 cross have pancreatitis
• Background Sensitivity: there is no correlation between pancreatitis and gastritis

digestive/alimentary system
• Background Sensitivity: a minor fraction of the mice from this F2 cross have gastritis
• Background Sensitivity: there is no correlation between pancreatitis and gastritis

liver/biliary system
• Background Sensitivity: a minor fraction of the mice from this F2 cross have inflammatory lesions in the liver
• Background Sensitivity: there some correlation between lung lesions and liver lesions

respiratory system
• Background Sensitivity: a minor fraction of the mice from this F2 cross have inflammatory lesions in the lung
• Background Sensitivity: there some correlation between lung lesions and liver lesions


Mouse Genome Informatics
hm6
    Airetm1.1Doi/Airetm1.1Doi
NOD.129S2(B6)-Airetm1.1Doi/Doi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: 79% of mice die between 6 and 14 weeks of age with the likely cause of death being inflammatory lesions of the lungs with generalized pneumoitis
• Background Sensitivity: over 95% of the mice die by 20 weeks of age

growth/size
• Background Sensitivity: mice are prone to losing weight between 5 and 15 weeks of age with weight loss correlating to the intensity of pancreas or lung inflammation

immune system
• Background Sensitivity: sialitis is observed in all mice by 20 weeks of age which is a much higher incidence than what is observed when the mutant allele is on the C57BL/6 or BALB/c backgrounds
• Background Sensitivity: gastritis occurs in 87% of mice by 20 weeks of age but is rarely observed when the mutant allele is on C57BL/6
• Background Sensitivity: all mice exhibit inflammation of the pancreas on this background while no inflammation is observed in C57BL/6 or BALB/c mice carrying this mutant allele
• Background Sensitivity: the lesions are highly localized within the pancreas and appear to progress from an initial extravasation into the perivascular connective tissue to a front of cell destruction that moves through the exocrine lobe
• Background Sensitivity: islet cells are spared from destruction and the mice remain normoglycemic through 20 weeks of age
• Background Sensitivity: all mice have inflammation of the prostate by 20 weeks of age (J:107432)
• Background Sensitivity: inflammation of the thyroid occurs in 54% of mice on the NOD background but is not observed in when the mutant allele is present on C57BL/6, BALB/c, or SJL backgrounds
• Background Sensitivity: mice generate autoantibodies with a reactivity that mirror the histopathology associated with this mouse strain
• Background Sensitivity: the autoantibodies generated on the NOD background target numerous tissues including the pancreas
• Background Sensitivity: the pancreas is not targeted by autoantibodies when the mutant allele is present on other genetic backgrounds
• Background Sensitivity: cornea inflammation occurs in 14% of mice of this background by 20 weeks of age but is not observed when the mutant allele is when the mutant allele is on the SJL or C57BL/6 background
• Background Sensitivity: liver inflammation is observed in 86% of mice by 20 weeks of age while no inflammation is present when the mutant allele is on the C57BL/6 background
• Background Sensitivity: 88% of mice exhibit inflammation of the ovaries on this background while no inflammation is observed in C57BL/6 mice carrying the mutant allele (J:107432)
• Background Sensitivity: lung inflammation is observed in 100% of mice by 20 weeks of age which is a much higher incidence than observed when the mutant allele is on the C57BL/6 background
• Background Sensitivity: lesions of the lung are severe enough to likely cause the runting and premature death associated with this strain

vision/eye
• Background Sensitivity: cornea inflammation occurs in 14% of mice of this background by 20 weeks of age but is not observed when the mutant allele is when the mutant allele is on the SJL or C57BL/6 background
• Background Sensitivity: retinal degeneration resulting from autoimmune disease occurs by 20 weeks of age in 93% of mice

endocrine/exocrine glands
• Background Sensitivity: sialitis is observed in all mice by 20 weeks of age which is a much higher incidence than what is observed when the mutant allele is on the C57BL/6 or BALB/c backgrounds
• Background Sensitivity: all mice exhibit inflammation of the pancreas on this background while no inflammation is observed in C57BL/6 or BALB/c mice carrying this mutant allele
• Background Sensitivity: the lesions are highly localized within the pancreas and appear to progress from an initial extravasation into the perivascular connective tissue to a front of cell destruction that moves through the exocrine lobe
• Background Sensitivity: islet cells are spared from destruction and the mice remain normoglycemic through 20 weeks of age
• Background Sensitivity: all mice have inflammation of the prostate by 20 weeks of age (J:107432)
• Background Sensitivity: inflammation of the thyroid occurs in 54% of mice on the NOD background but is not observed in when the mutant allele is present on C57BL/6, BALB/c, or SJL backgrounds

liver/biliary system
• Background Sensitivity: liver inflammation is observed in 86% of mice by 20 weeks of age while no inflammation is present when the mutant allele is on the C57BL/6 background

reproductive system
• Background Sensitivity: all mice have inflammation of the prostate by 20 weeks of age (J:107432)
• Background Sensitivity: 88% of mice exhibit inflammation of the ovaries on this background while no inflammation is observed in C57BL/6 mice carrying the mutant allele (J:107432)

respiratory system
• Background Sensitivity: lung inflammation is observed in 100% of mice by 20 weeks of age which is a much higher incidence than observed when the mutant allele is on the C57BL/6 background
• Background Sensitivity: lesions of the lung are severe enough to likely cause the runting and premature death associated with this strain

digestive/alimentary system
• Background Sensitivity: sialitis is observed in all mice by 20 weeks of age which is a much higher incidence than what is observed when the mutant allele is on the C57BL/6 or BALB/c backgrounds
• Background Sensitivity: gastritis occurs in 87% of mice by 20 weeks of age but is rarely observed when the mutant allele is on C57BL/6


Mouse Genome Informatics
hm7
    Airetm1.1Doi/Airetm1.1Doi
NOD.129S2-Airetm1.1Doi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands
• occurs in mice by 10 weeks of age
• mice 10 weeks of age have severe lymphocytic infiltration of the lacrimal glands
• mice 10 weeks have age have severe lymphocytic infiltration of the pancreas
• mice 25 weeks of age have intra-islet infiltration of lymphocytes
• severe thyroiditis is observed in mice 15 to 25 weeks in age
• there is increased percentage of CD4 T cells in the spleen that are activated based on surface marker expression (CD62Llo CD44hi)
• retinal lymphocytic infiltration occurs in the eye
• lymphocyte infiltrates are found in mice by 10 weeks of age

endocrine/exocrine glands
• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands
• mice 10 weeks of age have severe lymphocytic infiltration of the lacrimal glands
• mice 10 weeks have age have severe lymphocytic infiltration of the pancreas
• mice 25 weeks of age have intra-islet infiltration of lymphocytes
• severe thyroiditis is observed in mice 15 to 25 weeks in age

respiratory system
• lymphocyte infiltrates are found in mice by 10 weeks of age

vision/eye
• mice 10 weeks of age have severe lymphocytic infiltration of the lacrimal glands
• retinal lymphocytic infiltration occurs in the eye

digestive/alimentary system
• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands
• occurs in mice by 10 weeks of age

hematopoietic system
• there is increased percentage of CD4 T cells in the spleen that are activated based on surface marker expression (CD62Llo CD44hi)


Mouse Genome Informatics
hm8
    Airetm1.1Doi/Airetm1.1Doi
SJL.129S2-Airetm1.1Doi/Doi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• Background Sensitivity: sialitis is observed in all mice by 20 weeks of age which is a much higher incidence than what is observed when the mutant allele is on the C57BL/6 or BALB/c backgrounds
• Background Sensitivity: gastritis occurs in all mice by 20 weeks of age but is rarely observed when the mutant allele is on the C57BL/6 background
• 71% of mice exhibit inflammation of the pancreas on this background while no inflammation is observed in C57BL/6 or BALB/c mice carrying this mutant allele
• all mice have inflammation of the prostate by 20 weeks of age (J:107432)
• Background Sensitivity: mice generate autoantibodies with a reactivity that mirror the histopathology associated with this mouse strain
• Background Sensitivity: liver inflammation is observed in 83% of mice by 20 weeks of age while no inflammation is present when the mutant allele is on the C57BL/6 background
• Background Sensitivity: 50% of mice exhibit inflammation of the ovaries on this background while no inflammation is observed in C57BL/6 mice carrying the mutant allele (J:107432)
• Background Sensitivity: lung inflammation is observed in 100% of mice by 20 weeks of age which is a much higher incidence than observed when the mutant allele is on the C57BL/6 background

endocrine/exocrine glands
• Background Sensitivity: sialitis is observed in all mice by 20 weeks of age which is a much higher incidence than what is observed when the mutant allele is on the C57BL/6 or BALB/c backgrounds
• 71% of mice exhibit inflammation of the pancreas on this background while no inflammation is observed in C57BL/6 or BALB/c mice carrying this mutant allele
• all mice have inflammation of the prostate by 20 weeks of age (J:107432)

digestive/alimentary system
• Background Sensitivity: sialitis is observed in all mice by 20 weeks of age which is a much higher incidence than what is observed when the mutant allele is on the C57BL/6 or BALB/c backgrounds
• Background Sensitivity: gastritis occurs in all mice by 20 weeks of age but is rarely observed when the mutant allele is on the C57BL/6 background

liver/biliary system
• Background Sensitivity: liver inflammation is observed in 83% of mice by 20 weeks of age while no inflammation is present when the mutant allele is on the C57BL/6 background

reproductive system
• all mice have inflammation of the prostate by 20 weeks of age (J:107432)
• Background Sensitivity: 50% of mice exhibit inflammation of the ovaries on this background while no inflammation is observed in C57BL/6 mice carrying the mutant allele (J:107432)

respiratory system
• Background Sensitivity: lung inflammation is observed in 100% of mice by 20 weeks of age which is a much higher incidence than observed when the mutant allele is on the C57BL/6 background


Mouse Genome Informatics
ht9
    Airetm1Mand/Airetm1.1Doi
NOD.129-Airetm1Mand/Airetm1.1Doi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• weight loss is noted in mice starting at 6 weeks of age

immune system
• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands
• occurs in mice by 10 weeks of age
• mice 10 weeks of age have severe lymphocytic infiltration of the lacrimal glands
• mice 10 weeks have age have severe lymphocytic infiltration of the pancreas
• mice 25 weeks of age have intra-islet infiltration of lymphocytes
• severe thyroiditis is observed in mice 15 to 25 weeks in age
• there is increased percentage of CD4 T cells in the spleen that are activated based on surface marker expression (CD62Llo CD44hi)
• retinal lymphocytic infiltration occurs in the eye
• lymphocyte infiltrates are found in mice by 10 weeks of age

endocrine/exocrine glands
• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands
• mice 10 weeks of age have severe lymphocytic infiltration of the lacrimal glands
• mice 10 weeks have age have severe lymphocytic infiltration of the pancreas
• mice 25 weeks of age have intra-islet infiltration of lymphocytes
• severe thyroiditis is observed in mice 15 to 25 weeks in age

respiratory system
• lymphocyte infiltrates are found in mice by 10 weeks of age

digestive/alimentary system
• mice 10 weeks of age have severe lymphocytic infiltration of the salivary glands
• occurs in mice by 10 weeks of age

vision/eye
• mice 10 weeks of age have severe lymphocytic infiltration of the lacrimal glands
• retinal lymphocytic infiltration occurs in the eye

hematopoietic system
• there is increased percentage of CD4 T cells in the spleen that are activated based on surface marker expression (CD62Llo CD44hi)


Mouse Genome Informatics
cx10
    Airetm1.1Doi/Airetm1.1Doi
Tg(Ins2-TFRC/OVA)296Wehi/0
Tg(TcraTcrb)425Cbn/0

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• there is a slight reduction in the number of CD4 single positive thymocytes in the thymus compared to controls
• negative selection of CD 4 T cells bearing the transgenic TCR is impaired as evidenced by only a slight reduction of clonotypic T cells occuring in the thymus and spleen

hematopoietic system
• there is a slight reduction in the number of CD4 single positive thymocytes in the thymus compared to controls
• negative selection of CD 4 T cells bearing the transgenic TCR is impaired as evidenced by only a slight reduction of clonotypic T cells occuring in the thymus and spleen


Mouse Genome Informatics
cx11
    Airetm1.1Doi/Airetm1.1Doi
Il1r1tm1Imx/Il1r1+

involves: 129S2/SvPas * 129S7/SvEvBrd * NOD
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• inflammation damages the tear-secreting acinar cells and interlobular septa
• inflammation damages the tear-secreting acinar cells and interlobular septa
• mice exhibit an increase in acidified conjunctival goblet cells compared with wild-type mice
• however, the total number of goblet cells is normal
• desiccation and keratinization of the ocular surface
• ocular mucosal epithelia metaplasia
• ocular surface epitheliopathy
• squamous metaplasia
• progresses from desiccation and keratinization of the ocular surface

endocrine/exocrine glands
• inflammation damages the tear-secreting acinar cells and interlobular septa
• inflammation damages the tear-secreting acinar cells and interlobular septa

immune system
• inflammation damages the tear-secreting acinar cells and interlobular septa

Mouse Models of Human Disease
OMIM IDRef(s)
Sjogren Syndrome 270150 J:163691


Mouse Genome Informatics
cx12
    Airetm1.1Doi/Airetm1.1Doi
Il1r1tm1Imx/Il1r1tm1Imx

involves: 129S2/SvPas * 129S7/SvEvBrd * NOD
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• mostly CD4+ T cells
• mice exhibit an increase in acidified conjunctival goblet cells compared with wild-type mice that is not as severe as in Airetm1.1Doi homozygotes
• however, the total number of goblet cells is normal
• mice exhibit ocular mucosal epithelia metaplasia and ocular surface epitheliopathy that is not as severe as in Airetm1.1Doi homozygotes
• progresses from desiccation and keratinization of the ocular surface

immune system
• mostly CD4+ T cells

endocrine/exocrine glands
• mostly CD4+ T cells

Mouse Models of Human Disease
OMIM IDRef(s)
Sjogren Syndrome 270150 J:163691


Mouse Genome Informatics
cx13
    Airetm1.1Doi/Airetm1.1Doi
H2b/H2b

NOD.Cg-Airetm1.1Doi H2b/Doi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• Background Sensitivity: stomach inflammation is present regardless of the alleles found at the H2 locus

digestive/alimentary system
• Background Sensitivity: stomach inflammation is present regardless of the alleles found at the H2 locus

endocrine/exocrine glands
• Background Sensitivity: the pancreatitis associated with the Aire allele on the NOD background is absent when the H2 allele is present at homozygocity


Mouse Genome Informatics
cx14
    Airetm1.1Doi/Airetm1.1Doi
Idd3C57BL/6/Idd3C57BL/6
Idd5C57BL/10SnJ/Idd5C57BL/10SnJ

NOD.Cg-Idd3C57BL/6 Idd5C57BL/10SnJ Airetm1.1Doi/Doi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system

digestive/alimentary system

endocrine/exocrine glands
• Background Sensitivity: the pancreatitis associated with the Aire allele on the NOD background is much less severe when these alleles of Idd3 and Idd5 are present
• Background Sensitivity: the gastritis associated with the Aire allele on the NOD background is much less severe when these alleles of Idd3 and Idd5 are present