Phenotypes associated with this allele

• Allele Symbol: Sting1^em2Kaf
• Allele Name: endonuclease-mediated mutation 2, Katherine A Fitzgerald
• Allele ID: MGI:6306873
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sting1^em2Kaf/Sting1^em2Kaf	C57BL/6J-Sting1^em2Kaf	MGI:8355355
ht2	Sting1^em2Kaf/Sting1^+	C57BL/6J-Sting1^em2Kaf	MGI:8355356
cx3	Ifnar1^tm1Agt/Ifnar1^tm1Agt Sting1^em2Kaf/Sting1^+	involves: 129S2/SvPas * C57BL/6J	MGI:8355623
cx4	Irf3^tm1Ttg/Irf3^tm1Ttg Sting1^em2Kaf/Sting1^+	involves: 129S/SvEv * C57BL/6J	MGI:8355622
cx5	Mlkl^tm1.2Wsa/Mlkl^tm1.2Wsa Sting1^em2Kaf/Sting1^+	involves: C57BL/6 * C57BL/6J	MGI:8355627

Genotype
MGI:8355355

hm1

• Allelic Composition: Sting1^em2Kaf/Sting1^em2Kaf
• Genetic Background: C57BL/6J-Sting1^em2Kaf

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:274277 )

• no homozygous mice are obtained at E14

Genotype
MGI:8355356

ht2

• Allelic Composition: Sting1^em2Kaf/Sting1⁺
• Genetic Background: C57BL/6J-Sting1^em2Kaf

mortality/aging

premature death ( J:274277 )

• shorter lifespan, with mice starting to succumb by 4 weeks of age, and succumbing sooner over a 4-month period compared to Sting1^em1Kaf heterozygotes

prenatal lethality, incomplete penetrance ( J:274277 )

• when heterozygous males are mated to wild-type females, heterozygous offspring are born at less than the expected Mendelian frequency

hematopoietic system

small thymus ( J:274277 )

• smaller thymus by 4-6 weeks of age

enlarged spleen ( J:274277 )

• enlarged spleen by 4-6 weeks of age

increased common myeloid progenitor cell number ( J:274277 )

• the percentage of myeloid progenitors (Lin-sca1-ckit+) is increased in the bone marrow

extramedullary hematopoiesis ( J:274277 )

decreased B cell number ( J:274277 )

• 6-week-old mice show a reduced percentage and number of CD19+ B cells in the spleen and fewer B cells are seen at 16 weeks of age

• the B cells present in 6-week-old mice are activated

decreased immature B cell number ( J:274277 )

• the percentage of immature B220+AA4.1+ B cells is reduced in the bone marrow

decreased mature B cell number ( J:274277 )

• the percentage of mature B220+AA4.1- B cells is reduced in the bone marrow, with a greater reduction in mature B cells than in Sting1^em1Kaf heterozygotes

• mice show a greater reduction in the ratio of mature to immature B cells in the bone marrow than Sting1^em1Kaf heterozygotes

decreased T cell number ( J:274277 )

• spleen shows a reduction in percentage and number of T cell receptor-Beta+ (TCRb+) T cells compared to wild-type at 6 weeks of age and mice have fewer T cells than Sting1^em1Kaf heterozygotes

• remaining splenic T cells are activated and are more activated than T cells in the Sting1^em1Kaf heterozygotes

decreased thymocyte number ( J:274277 )

• total number of thymocytes, including the early CD4-CD8- double-negative thymocytes are reduced

increased myeloid cell number ( J:274277 )

• mice exhibit an increase in both the percentage and number of Ly6G^hi neutrophils in the spleen than in wild-type mice at 5 weeks of age and a greater percentage of neutrophils than the Sting1^em1Kaf heterozygotes

abnormal erythroid lineage cell morphology ( J:274277 )

• enlarged spleen shows increased percentage of Ter119+ erythroid lineage cells and increased percentage of immature erythrocytes (Ter119+ CD71+)

decreased erythrocyte cell number ( J:274277 )

• bone marrow exhibits reduced percentage of red blood cells

increased nucleated erythrocyte cell number ( J:274277 )

• enlarged spleen shows increased percentage of immature erythrocytes (Ter119+ CD71+)

immune system

small thymus ( J:274277 )

• smaller thymus by 4-6 weeks of age

enlarged spleen ( J:274277 )

• enlarged spleen by 4-6 weeks of age

decreased B cell number ( J:274277 )

• 6-week-old mice show a reduced percentage and number of CD19+ B cells in the spleen and fewer B cells are seen at 16 weeks of age

• the B cells present in 6-week-old mice are activated

decreased immature B cell number ( J:274277 )

• the percentage of immature B220+AA4.1+ B cells is reduced in the bone marrow

decreased mature B cell number ( J:274277 )

• the percentage of mature B220+AA4.1- B cells is reduced in the bone marrow, with a greater reduction in mature B cells than in Sting1^em1Kaf heterozygotes

• mice show a greater reduction in the ratio of mature to immature B cells in the bone marrow than Sting1^em1Kaf heterozygotes

decreased T cell number ( J:274277 )

• spleen shows a reduction in percentage and number of T cell receptor-Beta+ (TCRb+) T cells compared to wild-type at 6 weeks of age and mice have fewer T cells than Sting1^em1Kaf heterozygotes

• remaining splenic T cells are activated and are more activated than T cells in the Sting1^em1Kaf heterozygotes

decreased thymocyte number ( J:274277 )

• total number of thymocytes, including the early CD4-CD8- double-negative thymocytes are reduced

increased cytokine level ( J:274277 )

• cytokines such as RANTES, CP1, and MIP1b are induced at higher levels than in Sting1^em1Kaf heterozygotes

increased chemokine level ( J:274277 )

• several chemokines and cytokines, such as IP10, MIG, and GCSF are elevated in sera of 16-week-old mice

liver inflammation ( J:274277 )

• mice exhibit moderate inflammation in the liver

lung inflammation ( J:274277 )

homeostasis/metabolism

increased cytokine level ( J:274277 )

• cytokines such as RANTES, CP1, and MIP1b are induced at higher levels than in Sting1^em1Kaf heterozygotes

increased chemokine level ( J:274277 )

• several chemokines and cytokines, such as IP10, MIG, and GCSF are elevated in sera of 16-week-old mice

endocrine/exocrine glands

small thymus ( J:274277 )

• smaller thymus by 4-6 weeks of age

decreased thymocyte number ( J:274277 )

• total number of thymocytes, including the early CD4-CD8- double-negative thymocytes are reduced

growth/size/body

decreased body size ( J:274277 )

• mice exhibit a smaller body size than wild-type mice and are smaller than Sting1^em1Kaf heterozygotes

decreased body weight ( J:274277 )

enlarged spleen ( J:274277 )

• enlarged spleen by 4-6 weeks of age

liver/biliary system

liver inflammation ( J:274277 )

• mice exhibit moderate inflammation in the liver

reproductive system

abnormal parturition ( J:274277 )

♀ • females are poor breeders and when pregnant, frequently have problems delivering pups

reduced female fertility ( J:274277 )

♀ • females are poor breeders

respiratory system

lung inflammation ( J:274277 )

pulmonary fibrosis ( J:274277 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
STING-associated vasculopathy with onset in infancy		DOID:0111457	OMIM:615934	J:274277

Genotype
MGI:8355623

cx3

• Allelic Composition: Ifnar1^tm1Agt/Ifnar1^tm1Agt; Sting1^em2Kaf/Sting1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

mortality/aging

premature death ( J:274277 )

• mice exhibit a similar survival curve and shorter lifespan as single Sting1^em2Kaf heterozygotes, with mice starting to succumb by 4 weeks of age

hematopoietic system

decreased thymus weight ( J:274277 )

enlarged spleen ( J:274277 )

• splenomegaly due to accumulation of immature red blood cells

increased nucleated erythrocyte cell number ( J:274277 )

• accumulation of immature red blood cells in the spleen

increased neutrophil cell number ( J:274277 )

• an increase in percentage of neutrophils is similar to that seen in single Sting1^em2Kaf heterozygotes

decreased T cell number ( J:274277 )

• T cell loss, with activation of residual T cells that is comparable to levels in single Sting1^em2Kaf heterozygotes

immune system

abnormal immune system morphology ( J:274277 )

• immune defects are similar to that seen in single Sting1^em2Kaf heterozygotes and are not rescued

decreased thymus weight ( J:274277 )

enlarged spleen ( J:274277 )

• splenomegaly due to accumulation of immature red blood cells

increased neutrophil cell number ( J:274277 )

• an increase in percentage of neutrophils is similar to that seen in single Sting1^em2Kaf heterozygotes

decreased T cell number ( J:274277 )

• T cell loss, with activation of residual T cells that is comparable to levels in single Sting1^em2Kaf heterozygotes

endocrine/exocrine glands

decreased thymus weight ( J:274277 )

growth/size/body

enlarged spleen ( J:274277 )

• splenomegaly due to accumulation of immature red blood cells

Genotype
MGI:8355622

cx4

• Allelic Composition: Irf3^tm1Ttg/Irf3^tm1Ttg; Sting1^em2Kaf/Sting1⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6J

mortality/aging

premature death ( J:274277 )

• mice exhibit a similar survival curve and shorter lifespan as single Sting1^em2Kaf heterozygotes, with mice starting to succumb by 4 weeks of age

hematopoietic system

enlarged spleen ( J:274277 )

• splenomegaly due to accumulation of immature red blood cells

increased nucleated erythrocyte cell number ( J:274277 )

• accumulation of immature red blood cells in the spleen

growth/size/body

enlarged spleen ( J:274277 )

• splenomegaly due to accumulation of immature red blood cells

immune system

enlarged spleen ( J:274277 )

• splenomegaly due to accumulation of immature red blood cells

Genotype
MGI:8355627

cx5

• Allelic Composition: Mlkl^tm1.2Wsa/Mlkl^tm1.2Wsa; Sting1^em2Kaf/Sting1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J

immune system

abnormal immune system morphology ( J:274277 )

• mice exhibit similar immune abnormalities that are seen in single Sting1^em2Kaf heterozygotes