Phenotypes Associated with This Genotype

Genotype
MGI:3692382

• Allelic Composition: Dnase2a^tm1Osa/Dnase2a^tm2Osa; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * CBA

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

growth/size/body

postnatal growth retardation ( J:114982 )

• pI-pC treated mutants are growth retarded

immune system

abnormal macrophage morphology ( J:114982 )

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

abnormal cytokine level ( J:114982 )

• 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

increased circulating interleukin-18 level ( J:114982 )

• serum pI-pC treated mutants shows elevated levels of IL-18 protein

increased circulating tumor necrosis factor level ( J:114982 )

• serum of pI-pC treated mutants shows elevated levels of TNF-alpha before joints show abnormalities

joint inflammation ( J:114982 )

• 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

rheumatoid arthritis ( J:114982 )

• 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

anemia ( J:114982 )

• pI-pC treated mutants are slightly anemic

abnormal macrophage morphology ( J:114982 )

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

homeostasis/metabolism

abnormal blood homeostasis ( J:114982 )

• pI-pC treated mutants carry a low but significant level of DNA in serum

abnormal cytokine level ( J:114982 )

• 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

increased circulating interleukin-18 level ( J:114982 )

• serum pI-pC treated mutants shows elevated levels of IL-18 protein

increased circulating tumor necrosis factor level ( J:114982 )

• serum of pI-pC treated mutants shows elevated levels of TNF-alpha before joints show abnormalities

skeleton

joint inflammation ( J:114982 )

• 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

rheumatoid arthritis ( J:114982 )

• 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