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Phenotypes Associated with This Genotype
Genotype
MGI:3692382
Allelic
Composition
Dnase2atm1Osa/Dnase2atm2Osa
Tg(Mx1-cre)1Cgn/0
Genetic
Background
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dnase2atm1Osa mutation (2 available); any Dnase2a mutation (87 available)
Dnase2atm2Osa mutation (1 available); any Dnase2a mutation (87 available)
Tg(Mx1-cre)1Cgn mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• pI-pC treated mutants are growth retarded

immune system
• pI-pC treated mutants exhibit numerous abnormal macrophages that contain DNA in lysosomes in the bone marrow, spleen and other tissues
• affected joints of pI-pC treated mutants 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 pI-pC treated mutants shows elevated levels of IL-18 protein
• serum of pI-pC treated mutants shows elevated levels of TNF-alpha before joints show abnormalities
• joints of pI-pC treated mutants 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
• exhibit infiltration of subsynovial tissues by T cells and neutrophils
• poly(I)-poly(C) (pI-pC) treated mutants develop polyarthritis in a time-dependent manner; forelimbs and hindlimbs begin to swell 2-3 months after pI-pC treatment
• swelling first affects the digits, then the foot, and finally the wrists and ankles

hematopoietic system
• pI-pC treated mutants are slightly anemic
• pI-pC treated mutants exhibit numerous abnormal macrophages that contain DNA in lysosomes in the bone marrow, spleen and other tissues

homeostasis/metabolism
• pI-pC treated mutants carry a low but significant level of DNA in serum
• affected joints of pI-pC treated mutants 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 pI-pC treated mutants shows elevated levels of IL-18 protein
• serum of pI-pC treated mutants shows elevated levels of TNF-alpha before joints show abnormalities

skeleton
• joints of pI-pC treated mutants 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
• exhibit infiltration of subsynovial tissues by T cells and neutrophils
• poly(I)-poly(C) (pI-pC) treated mutants develop polyarthritis in a time-dependent manner; forelimbs and hindlimbs begin to swell 2-3 months after pI-pC treatment
• swelling first affects the digits, then the foot, and finally the wrists and ankles

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


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
04/09/2019
MGI 6.13
The Jackson Laboratory