Phenotypes Associated with This Genotype

Genotype
MGI:8355356

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

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

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