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Phenotypes Associated with This Genotype
Genotype
MGI:3526798
Allelic
Composition
Dnase2atm1Osa/Dnase2atm1Osa
Ifnar1tm1Agt/Ifnar1tm1Agt
Genetic
Background
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dnase2atm1Osa mutation (2 available); any Dnase2a mutation (87 available)
Ifnar1tm1Agt mutation (10 available); any Ifnar1 mutation (33 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body

immune system
• exhibit numerous abnormal macrophages that contain DNA in lysosomes in the bone marrow, spleen and other tissues
• increase in expression of IFN-beta in splenic tissue
• splenomegaly due to enlargement of the red pulp
• develop splenomegaly from 1 month of age, which becomes prominent as mutants age (J:114982)
• splenomegaly, with spleen sizes being 4-5 fold increased (J:238323)
• affected joints show 5-100 fold elevation of TNF-alpha, IL-1beta, IL-6, IL-10, IFN-beta, and IFN-gamma mRNA levels, the set of cytokines that are elevated in joints of humans with rheumatoid arthritis
• serum shows elevated levels of IL-18 protein
• serum shows elevated levels of TNF-alpha at 4-6 weeks of age, before joints show abnormalities; the extend of elevation decreases as mutants age (J:114982)
• presence of anti-cyclic citrullinated peptide antibodies
• level of anti-double-stranded DNA antibody is elevated 3-fold
• joints of show severe synovitis with villus proliferation accompanied by pannus formation; pannus fills the joint cavity, erodes cartilage, destroys bones, and occasionally penetrates the bone marrow (J:114982)
• exhibit infiltration of subsynovial tissues by T cells and neutrophils (J:114982)
• joints show severe signs of synovitis with hyperproliferation of synovial cells and massive immune cell infiltration at 15 months of age, associated with panus formation, cartilage destruction, and bone erosion (J:238323)
• develop polyarthritis as age; forelimbs and hindlimbs begin to swell at 2-3 months of age and swelling first affects the digits, then the foot and finally the wrists and ankles (J:114982)
• mice develop chronic polyarthritis that progresses with age (J:238323)
• joints show an increase in cleaved caspase-1, indicating signs of inflammasome activation (J:238323)
• expression of pro-inflammatory cytokines such as TNF, IL-6, and IL-1beta is increased both at protein and mRNA level in joints (J:238323)
• immune cell infiltrate is mainly dominated by presence of macrophages (J:238323)

hematopoietic system
• slightly anemic
• exhibit numerous abnormal macrophages that contain DNA in lysosomes in the bone marrow, spleen and other tissues
• increase in expression of IFN-beta in splenic tissue
• splenomegaly due to enlargement of the red pulp
• develop splenomegaly from 1 month of age, which becomes prominent as mutants age (J:114982)
• splenomegaly, with spleen sizes being 4-5 fold increased (J:238323)

homeostasis/metabolism
• carry a significant level of DNA in serum which decreases as mutants age
• affected joints show 5-100 fold elevation of TNF-alpha, IL-1beta, IL-6, IL-10, IFN-beta, and IFN-gamma mRNA levels, the set of cytokines that are elevated in joints of humans with rheumatoid arthritis
• serum shows elevated levels of IL-18 protein
• serum shows elevated levels of TNF-alpha at 4-6 weeks of age, before joints show abnormalities; the extend of elevation decreases as mutants age (J:114982)

skeleton
• joints of show severe synovitis with villus proliferation accompanied by pannus formation; pannus fills the joint cavity, erodes cartilage, destroys bones, and occasionally penetrates the bone marrow (J:114982)
• exhibit infiltration of subsynovial tissues by T cells and neutrophils (J:114982)
• joints show severe signs of synovitis with hyperproliferation of synovial cells and massive immune cell infiltration at 15 months of age, associated with panus formation, cartilage destruction, and bone erosion (J:238323)
• develop polyarthritis as age; forelimbs and hindlimbs begin to swell at 2-3 months of age and swelling first affects the digits, then the foot and finally the wrists and ankles (J:114982)
• mice develop chronic polyarthritis that progresses with age (J:238323)
• joints show an increase in cleaved caspase-1, indicating signs of inflammasome activation (J:238323)
• expression of pro-inflammatory cytokines such as TNF, IL-6, and IL-1beta is increased both at protein and mRNA level in joints (J:238323)
• immune cell infiltrate is mainly dominated by presence of macrophages (J:238323)

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
rheumatoid arthritis DOID:7148 OMIM:180300
J:114982 , J:238323


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