All Phenotypes Dnase2a<tm1Osa> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dnase2a^tm1Osa/Dnase2a^tm1Osa	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3040432
cn2	Dnase2a^tm1Osa/Dnase2a^tm2Osa Tg(Mx1-cre)1Cgn/0	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * CBA	MGI:3692382
cx3	Aim2^tm1.2Arte/Aim2^tm1.2Arte Dnase2a^tm1Osa/Dnase2a^tm1Osa Ifnar1^tm1Agt/Ifnar1^tm1Agt	involves: 129 * BALB/c * C57BL/6 * C57BL/6J	MGI:5823437
cx4	Dnase2a^tm1Osa/Dnase2a^tm1Osa Ifnar1^tm1Agt/Ifnar1^tm1Agt	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6	MGI:3526798
cx5	Dnase2a^tm1Osa/Dnase2a^tm1Osa Ifnar1^tm1Agt/Ifnar1^tm1Agt Xkr8^tm1.2Osa/Xkr8^tm1.2Osa	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6	MGI:7614309
cx6	Dffb^tm1Osa/Dffb^tm1Osa Dnase2a^tm1Osa/Dnase2a^tm1Osa	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3694082

Allelic Composition	Dnase2a^tm1Osa/Dnase2a^tm1Osa
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dnase2a^tm1Osa mutation (2 available); any Dnase2a mutation (92 available)

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

mortality/aging

lethality during fetal growth through weaning, complete penetrance ( J:69831 )

• no live homozygous mutant animals were recovered, although they were present at a frequency roughly consistent with Mendelian inheritance throughout embryonic development

hematopoietic system

abnormal thymus morphology ( J:81474 )

• many large abnormal foci containing macrophage with fragmented DNA

small thymus ( J:81474 )

thymus hypoplasia ( J:81474 )

• cellularity 29% of controls

abnormal erythropoiesis ( J:69831 )

• homozygous null mice displayed impaired definitive erythropoiesis in the fetal liver and spleen

• the numbers of CFU-E (colony-forming unit, erythroid) as well as BFU-E (burst-forming unit, erythroid), CFU-G (granulocyte), and CFU-M (macrophage) in the E12.5 fetal liver were similar between wild-type and homozygous null embryos

• diaminofluorene staining revealed that mutant erythroid cells were able to differentiate into hemoglobin-producing cells

• in colonies of CFU-E generated with either wild-type or homozygous null fetal liver cells, about 10% of cells were enucleated

• when homozygous null fetal liver cells were transferred into lethally-irradiated wild-type mice, mature red blood cells were generated from the mutant cells, suggesting that impairment of definitive erythropoiesis was due to a non-cell-autonomous effect

• histochemical analysis of E12.5 to E17.5 mutant fetal livers revealed reduced cellularity relative to wild-type, as well as the presence of abnormal foci of various sizes

• electron transmission microscopy combined with immunohistochemical analysis of E12.5 to E17.5 mutant fetal livers revealed accumulation of a large amount of DNA, as well as the presence of macrophage-like cells which were often surrounded by erythroid cells at various stages of differentiation

• these findings suggested that macrophage enzyme activity is required for degradation of nuclear DNA expelled during erythrocyte maturation

anemia ( J:69831 )

• some homozygous null embryos became paler than normal at E14.5, and all mutant embryos were severely anemic by E17.5; no other abnormalities besides anemia were observed at E17.5

decreased erythrocyte cell number ( J:69831 )

• up to E12.5, a normal level of vasculature was noted in the homozygous null embryos and yolk sac

• at E12.5, similar numbers of nucleated primitive erythrocytes were observed in the peripheral blood of wild-type and homozygous null embryos

• however, the number of mature erythrocytes in the peripheral blood of homozygous null embryos was less than 1/10th of that present in normal controls at E17.5

• no hemolysis was observed

increased nucleated erythrocyte cell number ( J:69831 , J:81474 )

• the peripheral blood of mutant embryos contained nucleated erythrocytes, which were not erythrosin-positive primitive erythrocytes, but appeared to be erythroblasts that had not undergone enucleation (J:69831)

immune system

abnormal thymus morphology ( J:81474 )

• many large abnormal foci containing macrophage with fragmented DNA

small thymus ( J:81474 )

thymus hypoplasia ( J:81474 )

• cellularity 29% of controls

endocrine/exocrine glands

abnormal thymus morphology ( J:81474 )

• many large abnormal foci containing macrophage with fragmented DNA

small thymus ( J:81474 )

thymus hypoplasia ( J:81474 )

• cellularity 29% of controls

Allelic Composition	Dnase2a^tm1Osa/Dnase2a^tm2Osa 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:
Dnase2a^tm1Osa mutation (2 available); any Dnase2a mutation (92 available)
Dnase2a^tm2Osa mutation (1 available); any Dnase2a mutation (92 available)
Tg(Mx1-cre)1Cgn mutation (7 available)

♀	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 )

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 )

• 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

Allelic Composition	Aim2^tm1.2Arte/Aim2^tm1.2Arte Dnase2a^tm1Osa/Dnase2a^tm1Osa Ifnar1^tm1Agt/Ifnar1^tm1Agt
Genetic Background	involves: 129 * BALB/c * C57BL/6 * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aim2^tm1.2Arte mutation (0 available); any Aim2 mutation (32 available)
Dnase2a^tm1Osa mutation (2 available); any Dnase2a mutation (92 available)
Ifnar1^tm1Agt mutation (11 available); any Ifnar1 mutation (59 available)

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

hematopoietic system

abnormal spleen morphology ( J:238323 )

• increase in expression of IFN-beta in splenic tissue

enlarged spleen ( J:238323 )

• splenomegaly, with spleen sizes being 4-5 fold increased

increased spleen weight ( J:238323 )

homeostasis/metabolism

increased circulating interleukin-10 level ( J:238323 )

increased circulating tumor necrosis factor level ( J:238323 )

immune system

abnormal spleen morphology ( J:238323 )

• increase in expression of IFN-beta in splenic tissue

enlarged spleen ( J:238323 )

• splenomegaly, with spleen sizes being 4-5 fold increased

increased spleen weight ( J:238323 )

increased circulating interleukin-10 level ( J:238323 )

increased circulating tumor necrosis factor level ( J:238323 )

increased autoantibody level ( J:238323 )

• presence of anti-cyclic citrullinated peptide antibodies

rheumatoid arthritis ( J:238323 )

• signs of polyarthritis are reduced compared to double Dnase2a and Ifnar1 homozygotes, although mice do show some arthritis development

• joints do not show an increase in cleaved caspase-1

• expression of pro-inflammatory cytokines, such as TNF, IL-6, and IL-1beta, is reduced both at protein and mRNA level in joints compared to double Dnase2a and Ifnar1 homozygotes

• mice show decreased macrophage infiltration in joints compared to double Dnase2a and Ifnar1 homozygotes

skeleton

rheumatoid arthritis ( J:238323 )

• signs of polyarthritis are reduced compared to double Dnase2a and Ifnar1 homozygotes, although mice do show some arthritis development

• joints do not show an increase in cleaved caspase-1

• expression of pro-inflammatory cytokines, such as TNF, IL-6, and IL-1beta, is reduced both at protein and mRNA level in joints compared to double Dnase2a and Ifnar1 homozygotes

• mice show decreased macrophage infiltration in joints compared to double Dnase2a and Ifnar1 homozygotes

growth/size/body

enlarged spleen ( J:238323 )

• splenomegaly, with spleen sizes being 4-5 fold increased

increased spleen weight ( J:238323 )

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

growth/size/body

postnatal growth retardation ( J:114982 )

enlarged spleen ( J:114982 , J:238323 )

• 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)

increased spleen weight ( J:238323 )

immune system

abnormal macrophage morphology ( J:114982 )

• exhibit numerous abnormal macrophages that contain DNA in lysosomes in the bone marrow, spleen and other tissues

abnormal spleen morphology ( J:238323 )

• increase in expression of IFN-beta in splenic tissue

enlarged spleen ( J:114982 , J:238323 )

• 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)

increased spleen weight ( J:238323 )

increased spleen red pulp amount ( J:114982 )

• splenomegaly due to enlargement of the red pulp

abnormal cytokine level ( J:114982 )

• 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

increased circulating interleukin-10 level ( J:238323 )

increased circulating interleukin-18 level ( J:114982 )

• serum shows elevated levels of IL-18 protein

increased circulating tumor necrosis factor level ( J:114982 , J:238323 )

• 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)

increased autoantibody level ( J:238323 )

• presence of anti-cyclic citrullinated peptide antibodies

increased anti-double stranded DNA antibody level ( J:114982 )

• level of anti-double-stranded DNA antibody is elevated 3-fold

joint inflammation ( J:114982 , J:238323 )

• 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)

rheumatoid arthritis ( J:114982 , 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

anemia ( J:114982 )

• slightly anemic

abnormal macrophage morphology ( J:114982 )

• exhibit numerous abnormal macrophages that contain DNA in lysosomes in the bone marrow, spleen and other tissues

abnormal spleen morphology ( J:238323 )

• increase in expression of IFN-beta in splenic tissue

enlarged spleen ( J:114982 , J:238323 )

• 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)

increased spleen weight ( J:238323 )

increased spleen red pulp amount ( J:114982 )

• splenomegaly due to enlargement of the red pulp

homeostasis/metabolism

abnormal blood homeostasis ( J:114982 )

• carry a significant level of DNA in serum which decreases as mutants age

abnormal cytokine level ( J:114982 )

increased circulating interleukin-10 level ( J:238323 )

increased circulating interleukin-18 level ( J:114982 )

• serum shows elevated levels of IL-18 protein

increased circulating tumor necrosis factor level ( J:114982 , J:238323 )

• 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

joint inflammation ( J:114982 , J:238323 )

• exhibit infiltration of subsynovial tissues by T cells and neutrophils (J:114982)

rheumatoid arthritis ( J:114982 , 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

Allelic Composition	Dnase2a^tm1Osa/Dnase2a^tm1Osa Ifnar1^tm1Agt/Ifnar1^tm1Agt Xkr8^tm1.2Osa/Xkr8^tm1.2Osa
Genetic Background	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dnase2a^tm1Osa mutation (2 available); any Dnase2a mutation (92 available)
Ifnar1^tm1Agt mutation (11 available); any Ifnar1 mutation (59 available)
Xkr8^tm1.2Osa mutation (2 available); any Xkr8 mutation (17 available)

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

reproductive system

abnormal Sertoli cell phagocytosis ( J:293092 )

• at 3 weeks of age, apoptotic germ cells are not engulfed by Sertoli cells; the number of Sertoli cells carrying undigested DNA (foci) is significantly lower than that in testes that are heterozygous for Xkr8^tm1.2Osa and homozygous for both Dnase2a^tm1Osa and Ifnar1^tm1Agt

• although abnormal foci are less abundant, many clusters of hematoxylin-positive materials are found in peripheral regions of the testicular tubes, suggesting that these represent unengulfed apoptotic bodies with condensed and fragmented nuclei

Allelic Composition	Dffb^tm1Osa/Dffb^tm1Osa Dnase2a^tm1Osa/Dnase2a^tm1Osa
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dffb^tm1Osa mutation (2 available); any Dffb mutation (27 available)
Dnase2a^tm1Osa mutation (2 available); any Dnase2a mutation (92 available)

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

growth/size/body

decreased body size ( J:81474 )

• slightly smaller than controls

hematopoietic system

abnormal thymus morphology ( J:81474 )

• many large abnormal foci containing macrophage with intact DNA filaments

small thymus ( J:81474 )

thymus hypoplasia ( J:81474 )

• cellularity 12% of controls

abnormal T cell differentiation ( J:81474 )

• T cell development inhibited at an early progenitor stage

increased double-negative T cell number ( J:81474 )

decreased double-positive T cell number ( J:81474 )

• about 1/3 the level seen in controls

anemia ( J:81474 )

immune system

abnormal thymus morphology ( J:81474 )

• many large abnormal foci containing macrophage with intact DNA filaments

small thymus ( J:81474 )

thymus hypoplasia ( J:81474 )

• cellularity 12% of controls

abnormal T cell differentiation ( J:81474 )

• T cell development inhibited at an early progenitor stage

increased double-negative T cell number ( J:81474 )

decreased double-positive T cell number ( J:81474 )

• about 1/3 the level seen in controls

endocrine/exocrine glands

abnormal thymus morphology ( J:81474 )

• many large abnormal foci containing macrophage with intact DNA filaments

small thymus ( J:81474 )

thymus hypoplasia ( J:81474 )

• cellularity 12% of controls

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