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Phenotypes Associated with This Genotype
Genotype
MGI:3843817
Allelic
Composition
Il6sttm1Thir/Il6sttm1Thir
Genetic
Background
involves: 129 * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il6sttm1Thir mutation (1 available); any Il6st mutation (30 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• mice develop RA starting at 8 months of age
• incidence is about 45% between 11 and 15 months of age, and 100% in mice over 16 months of age
• RA includes swelling and redness of the paws and limited mobility of the ankle or wrist joints
• joints have severe synovitis with destructive changes including marked proliferation of the synovium, infiltration of inflammatory cells, fibrin deposits and severe bone destruction
• the elbows and knees are affected symmetrically in many diseased mice and become rigid
• severity scores are significantly higher in female mice than males (13.5 in year-old females versus 9.6 in year-old males)
• osteoporosis is noted around inflamed joints of older mice

immune system
• injection with the T cell superantigen SEB does not cause clonal deletion of T-cells bearing Vbeta8 TCR chains as it does in wild-type mice
• inhibition of activation induced cell death by IL-6 is almost three times greater than in wild-type T cells
• in older mice with arthritis, the frequency of double-negative thymocytes is increased by 40 fold
• this population included B cells, plasma cells and dendritic cells
• in older mice with arthritis, the frequency of double-positive thymocytes is reduced by 40 fold
• decreases in this population are observed starting at 18 weeks of age before arthritis as set in
• increased numbers of neutrophils are found in the lymph nodes of mice with arthritis
• almost all CD4+ T cells bear activation or memory markers
• there is a three-fold increase in single-positive thymocytes of older mice with arthritis
• increases in this population are observed starting at 18 weeks of age before arthritis as set in
• IgA levels are slightly elevated in mice one year of age
• IgG1 levels are slightly elevated in mice one year of age
• IgG2a levels are slightly elevated in female mice one year of age
• IgG2b levels are slightly elevated in male mice one year of age
• T cells from lymph nodes of non-arthritic mice have higher rates of proliferation in response to anti-CD3 treatment than controls
• thymocytes from 12 week old mice hyper-proliferate in response to anti-CD3 treatment
• 1 year old mice have elevated levels of rheumatoid factor (Ig class)
• 1 year old mice have elevated levels of anti-ribonuclear protein antibodies with higher levels found in females
• 1 year old mice have elevated levels of anti-dsDNA antibodies with higher levels found in females
• 1 year old mice have elevated levels of anti-ssDNA antibodies with higher levels found in females
• mice develop RA starting at 8 months of age
• incidence is about 45% between 11 and 15 months of age, and 100% in mice over 16 months of age
• RA includes swelling and redness of the paws and limited mobility of the ankle or wrist joints
• joints have severe synovitis with destructive changes including marked proliferation of the synovium, infiltration of inflammatory cells, fibrin deposits and severe bone destruction
• the elbows and knees are affected symmetrically in many diseased mice and become rigid
• severity scores are significantly higher in female mice than males (13.5 in year-old females versus 9.6 in year-old males)

hematopoietic system
• injection with the T cell superantigen SEB does not cause clonal deletion of T-cells bearing Vbeta8 TCR chains as it does in wild-type mice
• inhibition of activation induced cell death by IL-6 is almost three times greater than in wild-type T cells
• in older mice with arthritis, the frequency of double-negative thymocytes is increased by 40 fold
• this population included B cells, plasma cells and dendritic cells
• in older mice with arthritis, the frequency of double-positive thymocytes is reduced by 40 fold
• decreases in this population are observed starting at 18 weeks of age before arthritis as set in
• increased numbers of neutrophils are found in the lymph nodes of mice with arthritis
• almost all CD4+ T cells bear activation or memory markers
• there is a three-fold increase in single-positive thymocytes of older mice with arthritis
• increases in this population are observed starting at 18 weeks of age before arthritis as set in
• IgA levels are slightly elevated in mice one year of age
• IgG1 levels are slightly elevated in mice one year of age
• IgG2a levels are slightly elevated in female mice one year of age
• IgG2b levels are slightly elevated in male mice one year of age
• T cells from lymph nodes of non-arthritic mice have higher rates of proliferation in response to anti-CD3 treatment than controls
• thymocytes from 12 week old mice hyper-proliferate in response to anti-CD3 treatment

endocrine/exocrine glands
• thymocytes from 12 week old mice hyper-proliferate in response to anti-CD3 treatment

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
rheumatoid arthritis DOID:7148 OMIM:180300
J:133059


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
04/16/2019
MGI 6.13
The Jackson Laboratory