Phenotypes associated with this allele

• Allele Symbol: Gt(ROSA)26Sor^{tm1(OVAL/fla,GFP)Vnce}
• Allele Name: targeted mutation 1, Russell E Vance
• Allele ID: MGI:6196853
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gt(ROSA)26Sor^tm1(OVAL/fla,GFP)Vnce/Gt(ROSA)26Sor^+ Lyz2^tm1(cre)Ifo/Lyz2^+ Pycard^tm1Vmd/Pycard^tm1Vmd	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6196858
cn2	Gt(ROSA)26Sor^tm1(OVAL/fla,GFP)Vnce/Gt(ROSA)26Sor^+ Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:6196856
cn3	Gt(ROSA)26Sor^tm1(OVAL/fla,GFP)Vnce/Gt(ROSA)26Sor^+ Lyz2^tm1(cre)Ifo/Lyz2^+ Nlrc4^tm1Vmd/Nlrc4^tm1Vmd	involves: 129P2/OlaHsd * C57BL/6J * C57BL/6NCrl	MGI:6196855
cn4	Gt(ROSA)26Sor^tm1(OVAL/fla,GFP)Vnce/Gt(ROSA)26Sor^+ Tg(S100A8-cre,-EGFP)1Ilw/0	involves: C3H * C57BL/6 * C57BL/6J	MGI:6196860
cn5	Gt(ROSA)26Sor^tm1(OVAL/fla,GFP)Vnce/Gt(ROSA)26Sor^+ Tg(Itgax-cre)1-1Reiz/0	involves: C3H * C57BL/6 * C57BL/6J	MGI:6196862

Genotype
MGI:6196858

cn1

• Allelic Composition: Gt(ROSA)26Sor^{tm1(OVAL/fla,GFP)Vnce}/Gt(ROSA)26Sor⁺; Lyz2^tm1(cre)Ifo/Lyz2⁺; Pycard^tm1Vmd/Pycard^tm1Vmd
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J

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

growth/size/body

growth/size/body region phenotype ( J:260047 )

N • mice show normal weight gain at 10 weeks of age

homeostasis/metabolism

increased circulating interferon-gamma level ( J:260047 )

• slight increase in IFN-gamma levels

increased circulating interleukin-6 level ( J:260047 )

• slight increase in IL-6 levels

increased circulating tumor necrosis factor level ( J:260047 )

• slight increase in TNF levels

immune system

immune system phenotype ( J:260047 )

N • mice show no joint inflammation at 10 weeks of age, cytokine levels (such as IL-1 alpha, IL-1 beta, and MCP-1) are severely reduced, and the autoinflammatory disease seen in Gt(ROSA)26Sor^{tm1(OVAL/fla-GFP)Vnce} and Lyz2^tm1(cre)Ifo expressing mice is almost entirely ameliorated

increased circulating interferon-gamma level ( J:260047 )

• slight increase in IFN-gamma levels

increased circulating interleukin-6 level ( J:260047 )

• slight increase in IL-6 levels

increased circulating tumor necrosis factor level ( J:260047 )

• slight increase in TNF levels

Genotype
MGI:6196856

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm1(OVAL/fla,GFP)Vnce}/Gt(ROSA)26Sor⁺; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

growth/size/body

decreased body size ( J:260047 )

• mice are runted prior to weaning

decreased body weight ( J:260047 )

• mice exhibit lower body weights throughout life

• mice treated with an alpha IL-1R blocking antibody show weight gain

enlarged spleen ( J:260047 )

• sick mice exhibit enlarged spleen

digestive/alimentary system

small intestinal inflammation ( J:260047 )

• pronounced neutrophilia is seen in the duodenums, with neutrophilic infiltration of the submucosa and lamina propria that extends into the underlying muscularis externa

hematopoietic system

enlarged spleen ( J:260047 )

• sick mice exhibit enlarged spleen

anemia ( J:260047 )

decreased hematocrit ( J:260047 )

increased neutrophil cell number ( J:260047 )

• pronounced neutrophilia is seen in the joints, duodenums, and kidney glomeruli

• increase in neutrophils in the peripheral blood of sick mice compared to healthy littermates

• increase in levels of neutrophils in spleen, and in peripheral and mesenteric lymph nodes

• mice treated with an alpha IL-1R blocking antibody show decreased levels of neutrophils in both the spleen and lymph nodes

increased T cell number ( J:260047 )

• slight increase of T cells in the spleen, however there are no changes in T cells in the lymph nodes

decreased lymphocyte cell number ( J:260047 )

• decrease in blood lymphocytes

decreased B cell number ( J:260047 )

• B cell numbers are modestly decreased in the lymph nodes

increased monocyte cell number ( J:260047 )

• increase in monocytes in the peripheral blood of the sick mice compared to healthy littermates

• increase in levels of monocytes in spleen, and in peripheral and mesenteric lymph nodes

• mice treated with an alpha IL-1R blocking antibody show decreased levels of monocytes in both the spleen and lymph nodes

homeostasis/metabolism

abnormal circulating cytokine level ( J:260047 )

• serum levels of cytokines and chemokines (IL-1 alpha, IL-1 beta, IFN-gamma, IL-6, MCP-1) are elevated

• mice treated with an alpha IL-1R blocking antibody show decreased IL-1bbeta, MCP-1, and TNF levels, however, levels of IL-18 are unchanged

joint swelling ( J:260047 )

• mice develop severe limb swelling, most noticeably in the tibiotarsal (heel) joint

• tibiotarsal joint swelling is 100% penetrant, although age of onset varies, beginning as early as 4 weeks or as late as 10 weeks of age

• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint

• mice treated with an alpha IL-1R blocking antibody show decreased tibiotarsal joint swelling

immune system

enlarged spleen ( J:260047 )

• sick mice exhibit enlarged spleen

increased neutrophil cell number ( J:260047 )

• pronounced neutrophilia is seen in the joints, duodenums, and kidney glomeruli

• increase in neutrophils in the peripheral blood of sick mice compared to healthy littermates

• increase in levels of neutrophils in spleen, and in peripheral and mesenteric lymph nodes

• mice treated with an alpha IL-1R blocking antibody show decreased levels of neutrophils in both the spleen and lymph nodes

increased T cell number ( J:260047 )

• slight increase of T cells in the spleen, however there are no changes in T cells in the lymph nodes

decreased lymphocyte cell number ( J:260047 )

• decrease in blood lymphocytes

decreased B cell number ( J:260047 )

• B cell numbers are modestly decreased in the lymph nodes

increased monocyte cell number ( J:260047 )

• increase in monocytes in the peripheral blood of the sick mice compared to healthy littermates

• increase in levels of monocytes in spleen, and in peripheral and mesenteric lymph nodes

• mice treated with an alpha IL-1R blocking antibody show decreased levels of monocytes in both the spleen and lymph nodes

abnormal circulating cytokine level ( J:260047 )

• serum levels of cytokines and chemokines (IL-1 alpha, IL-1 beta, IFN-gamma, IL-6, MCP-1) are elevated

• mice treated with an alpha IL-1R blocking antibody show decreased IL-1bbeta, MCP-1, and TNF levels, however, levels of IL-18 are unchanged

enlarged lymph nodes ( J:260047 )

• sick mice exhibit enlarged lymph nodes

increased inflammatory response ( J:260047 )

• mice exhibit systemic inflammation, with nearly all tissues showing neutrophilic infiltration

small intestinal inflammation ( J:260047 )

• pronounced neutrophilia is seen in the duodenums, with neutrophilic infiltration of the submucosa and lamina propria that extends into the underlying muscularis externa

joint inflammation ( J:260047 )

• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint

glomerulonephritis ( J:260047 )

• mice show varying degrees of kidney damage, with some mice having fibrin and neutrophil accumulation within the glomeruli indicating necrotizing glomerulonephritis, while others have some glomeruli with only thickened membranes

renal/urinary system

abnormal renal glomerulus morphology ( J:260047 )

• some mice exhibit glomeruli with only thickened membranes

glomerulonephritis ( J:260047 )

• mice show varying degrees of kidney damage, with some mice having fibrin and neutrophil accumulation within the glomeruli indicating necrotizing glomerulonephritis, while others have some glomeruli with only thickened membranes

skeleton

joint swelling ( J:260047 )

• mice develop severe limb swelling, most noticeably in the tibiotarsal (heel) joint

• tibiotarsal joint swelling is 100% penetrant, although age of onset varies, beginning as early as 4 weeks or as late as 10 weeks of age

• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint

• mice treated with an alpha IL-1R blocking antibody show decreased tibiotarsal joint swelling

joint inflammation ( J:260047 )

• substantial neutrophilic infiltration with slight to severe bone and cartilage erosion is seen in the tibiotarsal joint

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary immunodeficiency disease		DOID:612	OMIM:242850 OMIM:PS300755	J:260047

Genotype
MGI:6196855

cn3

• Allelic Composition: Gt(ROSA)26Sor^{tm1(OVAL/fla,GFP)Vnce}/Gt(ROSA)26Sor⁺; Lyz2^tm1(cre)Ifo/Lyz2⁺; Nlrc4^tm1Vmd/Nlrc4^tm1Vmd
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * C57BL/6NCrl

immune system

immune system phenotype ( J:260047 )

N • neutrophilic inflammation is not apparent

skeleton

skeleton phenotype ( J:260047 )

N • mice exhibit normal joints

Genotype
MGI:6196860

cn4

• Allelic Composition: Gt(ROSA)26Sor^{tm1(OVAL/fla,GFP)Vnce}/Gt(ROSA)26Sor⁺; Tg(S100A8-cre,-EGFP)1Ilw/0
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6J

growth/size/body

decreased body size ( J:260047 )

• mice are runted

decreased body weight ( J:260047 )

• mice treated with an alpha IL-1R blocking antibody show weight gain

hematopoietic system

increased neutrophil cell number ( J:260047 )

• increase in neutrophils in the spleen and lymph nodes

increased monocyte cell number ( J:260047 )

• increase in monocytes in the spleen and lymph nodes

homeostasis/metabolism

abnormal circulating cytokine level ( J:260047 )

• mice exhibit increased cytokine levels, with IL-18 having the greatest increase

increased circulating interleukin-18 level ( J:260047 )

joint swelling ( J:260047 )

• mice develop joint swelling

• mice treated with an alpha IL-1R blocking antibody show deceased joint swelling

immune system

increased neutrophil cell number ( J:260047 )

• increase in neutrophils in the spleen and lymph nodes

increased monocyte cell number ( J:260047 )

• increase in monocytes in the spleen and lymph nodes

abnormal circulating cytokine level ( J:260047 )

• mice exhibit increased cytokine levels, with IL-18 having the greatest increase

increased circulating interleukin-18 level ( J:260047 )

skeleton

joint swelling ( J:260047 )

• mice develop joint swelling

• mice treated with an alpha IL-1R blocking antibody show deceased joint swelling

Genotype
MGI:6196862

cn5

• Allelic Composition: Gt(ROSA)26Sor^{tm1(OVAL/fla,GFP)Vnce}/Gt(ROSA)26Sor⁺; Tg(Itgax-cre)1-1Reiz/0
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6J

growth/size/body

decreased body size ( J:260047 )

• mice are runted

hematopoietic system

increased neutrophil cell number ( J:260047 )

• mice exhibit elevation of neutrophils in tissues

increased monocyte cell number ( J:260047 )

• mice exhibit elevation of monocytes in tissues

immune system

increased neutrophil cell number ( J:260047 )

• mice exhibit elevation of neutrophils in tissues

increased monocyte cell number ( J:260047 )

• mice exhibit elevation of monocytes in tissues

skeleton

skeleton phenotype ( J:260047 )

N • mice do not develop joint swellings