Phenotypes associated with this allele

• Allele Symbol: Sting1^em1Jmin
• Allele Name: endonuclease-mediated mutation 1, Jonathan Miner
• Allele ID: MGI:6287305
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sting1^em1Jmin/Sting1^em1Jmin	involves: C57BL/6N	MGI:6302787
ht2	Sting1^em1Jmin/Sting1^+	involves: C57BL/6N	MGI:6302788
cn3	Arfgap2^tm1c(EUCOMM)Hmgu/Arfgap2^tm1c(EUCOMM)Hmgu Sting1^em1Jmin/Sting1^em1Jmin Commd10^Tg(Vav1-icre)A2Kio/Commd10^+	Not Specified	MGI:8207802
cx4	Irf3^tm1Ttg/Irf3^tm1Ttg Sting1^em1Jmin/Sting1^em1Jmin	involves: 129S/SvEv * C57BL/6N	MGI:6302792

Genotype
MGI:6302787

hm1

• Allelic Composition: Sting1^em1Jmin/Sting1^em1Jmin
• Genetic Background: involves: C57BL/6N

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

mortality/aging

prenatal lethality, complete penetrance ( J:251372 )

• mice do not survive gestation

Genotype
MGI:6302788

ht2

• Allelic Composition: Sting1^em1Jmin/Sting1⁺
• Genetic Background: involves: C57BL/6N

growth/size/body

enlarged spleen ( J:251372 )

hematopoietic system

decreased single-positive T cell number ( J:251372 )

• spleens show reduced numbers of T cells, which is more severe for CD8+ T cells than for CD4+ T cells, indicating T cell cytopenia

increased myeloid cell number ( J:251372 )

• spleens show an expansion of Ly6G+ myeloid cells and immature myeloid cells

abnormal spleen morphology ( J:251372 )

• abnormal spleen architecture

enlarged spleen ( J:251372 )

increased IgM level ( J:251372 )

• 3 of 5 mice produce higher levels of IgM but not IgG autoantibodies

homeostasis/metabolism

abnormal lung thrombosis ( J:251372 )

• lungs show organized thrombosis in pulmonary blood vessels

pleural effusion ( J:251372 )

abnormal cytokine level ( J:251372 )

• 4-6 month old mice exhibit elevated levels of multiple cytokines and chemokines, including TNF, IL-17a, IL-13, G-CSF, MIP-1alpha, MIP-1beta, MCP-1, and IL-10

increased circulating interleukin-10 level ( J:251372 )

• in 4-6 month old mice

increased circulating interleukin-13 level ( J:251372 )

• in 4-6 month old mice

increased circulating tumor necrosis factor level ( J:251372 )

• in 4-6 month old mice

immune system

decreased single-positive T cell number ( J:251372 )

• spleens show reduced numbers of T cells, which is more severe for CD8+ T cells than for CD4+ T cells, indicating T cell cytopenia

abnormal spleen morphology ( J:251372 )

• abnormal spleen architecture

enlarged spleen ( J:251372 )

increased IgM level ( J:251372 )

• 3 of 5 mice produce higher levels of IgM but not IgG autoantibodies

abnormal cytokine level ( J:251372 )

• 4-6 month old mice exhibit elevated levels of multiple cytokines and chemokines, including TNF, IL-17a, IL-13, G-CSF, MIP-1alpha, MIP-1beta, MCP-1, and IL-10

increased circulating interleukin-10 level ( J:251372 )

• in 4-6 month old mice

increased circulating interleukin-13 level ( J:251372 )

• in 4-6 month old mice

increased circulating tumor necrosis factor level ( J:251372 )

• in 4-6 month old mice

lung inflammation ( J:251372 )

• lungs show chronic perivascular inflammation with heterogeneous immune cell infiltration

• immune cells consist predominantly of CD19+ B cells and CD11b+ myeloid cells, with smaller numbers of CD4+ and CD8+ T cells

• however, pulmonary fibrosis is not seen

integument

skin lesions ( J:251372 )

• skin lesions show mixed immune cell infiltration, ulceration, and scarring

spontaneous skin ulceration ( J:251372 )

• ulcerative skin lesions of the extremities are seen in 5 mice and on the head in 1 mouse

respiratory system

pleural effusion ( J:251372 )

lung inflammation ( J:251372 )

• lungs show chronic perivascular inflammation with heterogeneous immune cell infiltration

• immune cells consist predominantly of CD19+ B cells and CD11b+ myeloid cells, with smaller numbers of CD4+ and CD8+ T cells

• however, pulmonary fibrosis is not seen

respiratory distress ( J:251372 )

• severe respiratory distress occurs frequently

• severe respiratory distress is sometimes seen during late pregnancy in dams that are unable to survive labor

renal/urinary system

renal/urinary system phenotype ( J:251372 )

N • mice show no evidence of inflamed or abnormal glomeruli

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
STING-associated vasculopathy with onset in infancy		DOID:0111457	OMIM:615934	J:251372

Genotype
MGI:8207802

cn3

• Allelic Composition: Arfgap2^{tm1c(EUCOMM)Hmgu}/Arfgap2^{tm1c(EUCOMM)Hmgu}; Sting1^em1Jmin/Sting1^em1Jmin; Commd10^{Tg(Vav1-icre)A2Kio}/Commd10⁺
• Genetic Background: Not Specified

immune system

decreased effector memory CD4-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant decrease in the numbers of CD4+ effector T cells (Teff, CD3+ CD4+CD44+ CD62L-) and the frequency of effector CD4+ T cells, relative to CD4+ T cells, in spleen

increased CD4-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant increase in the frequency of CD4+ T cells, relative to total CD3+ cells, and of naive CD4+ T cells (CD3+ CD4+ CD44-CD62L+), relative to CD4+ T cells, in spleen

increased CD4-positive, alpha-beta memory T cell number ( J:363611 )

• mice show a significant increase in the frequency of memory CD4+ T cells (CD3+ CD4+CD44+ CD62L+), relative to CD4+ T cells, in spleen

decreased CD8-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant decrease in the frequency of CD8+ T cells, relative to total CD3+ cells, in spleen

increased regulatory T cell number ( J:363611 )

• mice show a significant increase in the frequency of FoxP3+ regulatory T cells (Tregs), relative to CD4+ T cells, in spleen

abnormal splenic cell ratio ( J:363611 )

• mice show a significant increase in the ratio of CD4+ to CD8+ T cells along with a significant decrease in the ratio of Teff to Treg cells in spleen

decreased interferon-gamma secretion ( J:363611 )

• mice show a 6-fold decrease of interferon-gamma in lung homogenates

decreased interleukin-1 beta secretion ( J:363611 )

• mice show a 4-fold decrease of interleukin-1 beta levels in lung homogenates

decreased susceptibility to autoimmune disorder ( J:363611 )

• mice show marked amelioration of STING-associated autoinflammation and lung disease with ~4- and ~6-fold reductions in levels of IL-1beta and IFN-gamma, as well as ~170-, ~30, and ~12-fold reductions in mRNA levels of Cxcl9, Cxcl10, and Ccl5, respectively, with corresponding reductions in chemokine protein levels in the lungs relative to SAVI mice homozygous for Arfgap2 but without Cre

hematopoietic system

decreased effector memory CD4-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant decrease in the numbers of CD4+ effector T cells (Teff, CD3+ CD4+CD44+ CD62L-) and the frequency of effector CD4+ T cells, relative to CD4+ T cells, in spleen

increased CD4-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant increase in the frequency of CD4+ T cells, relative to total CD3+ cells, and of naive CD4+ T cells (CD3+ CD4+ CD44-CD62L+), relative to CD4+ T cells, in spleen

increased CD4-positive, alpha-beta memory T cell number ( J:363611 )

• mice show a significant increase in the frequency of memory CD4+ T cells (CD3+ CD4+CD44+ CD62L+), relative to CD4+ T cells, in spleen

decreased CD8-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant decrease in the frequency of CD8+ T cells, relative to total CD3+ cells, in spleen

increased regulatory T cell number ( J:363611 )

• mice show a significant increase in the frequency of FoxP3+ regulatory T cells (Tregs), relative to CD4+ T cells, in spleen

abnormal splenic cell ratio ( J:363611 )

• mice show a significant increase in the ratio of CD4+ to CD8+ T cells along with a significant decrease in the ratio of Teff to Treg cells in spleen

Genotype
MGI:6302792

cx4

• Allelic Composition: Irf3^tm1Ttg/Irf3^tm1Ttg; Sting1^em1Jmin/Sting1^em1Jmin
• Genetic Background: involves: 129S/SvEv * C57BL/6N

hematopoietic system

decreased single-positive T cell number ( J:251372 )

• the percent and absolute number of CD8+ T cells in spleen is reduced to a similar level as in single Sting1^em1Jmin homozygotes

increased myeloid cell number ( J:251372 )

• spleen shows a similar increase in the number of Ly6G+ and Ly6C+ myeloid cell populations as in single Sting1^em1Jmin homozygotes

immune system

decreased single-positive T cell number ( J:251372 )

• the percent and absolute number of CD8+ T cells in spleen is reduced to a similar level as in single Sting1^em1Jmin homozygotes

lung inflammation ( J:251372 )

• mice exhibit a similar level of perivascular immune cell infiltration as single Sting1^em1Jmin homozygotes

respiratory system

lung inflammation ( J:251372 )

• mice exhibit a similar level of perivascular immune cell infiltration as single Sting1^em1Jmin homozygotes