Phenotypes associated with this allele

• Allele Symbol: Rubcn^em1Dgre
• Allele Name: endonuclease-mediated mutation 1, Douglas R Green
• Allele ID: MGI:6196512
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rubcn^em1Dgre/Rubcn^em1Dgre	C57BL/6-Rubcn^em1Dgre	MGI:6196876
hm2	Rubcn^em1Dgre/Rubcn^em1Dgre	involves: C57BL/6 * C57BL/6N	MGI:6287978
cx3	Rubcn^em1Dgre/Rubcn^em1Dgre Tg(CAG-EGFP/Map1lc3b)53Nmz/0	involves: C57BL/6 * C57BL/6J * C57BL/6N * C57BL/6NCrlj * DBA/2	MGI:6196878
cx4	Rubcn^em1Dgre/Rubcn^em1Dgre Tg(CAG-EGFP/Map1lc3b)53Nmz/0	involves: C57BL/6 * C57BL/6N * DBA/2	MGI:6287979

Genotype
MGI:6196876

hm1

• Allelic Composition: Rubcn^em1Dgre/Rubcn^em1Dgre
• Genetic Background: C57BL/6-Rubcn^em1Dgre

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

hematopoietic system

hematopoietic system phenotype ( J:261225 )

N • normal numbers of B, T and NK cells in spleens and lymph nodes and normal T cell subsets in thymi

abnormal macrophage physiology ( J:261225 )

• reduced recruitment of Becn1, Uvrag, Pick3c3 (VPS34), Map1lc3 (LC3-II) and Atg7 to LAP (LC3-associated phagocytosis)-engaged phagosomes

• no recruitment of Atg5-12 and Atg16l to LAP (LC3-associated phagocytosis)-engaged phagosomes

• lack of phosphatidylinositol 3-phosphate generation by Pick3c3 (VPS34) associated with LAP (LC3-associated phagocytosis)-engaged phagosomes

• failure to produce ROS (reactive oxygen species) upon zymosan stimulation

• lack of phosphorylated Ncf4 (p-p40PHOX) in LAP (LC3-associated phagocytosis)-engaged phagosomes

• levels of Cyba (p22PHOX) in LAP (LC3-associated phagocytosis)-engaged phagosomes

immune system

immune system phenotype ( J:261225 )

N • normal numbers of B, T and NK cells in spleens and lymph nodes and normal T cell subsets in thymi

abnormal macrophage physiology ( J:261225 )

• reduced recruitment of Becn1, Uvrag, Pick3c3 (VPS34), Map1lc3 (LC3-II) and Atg7 to LAP (LC3-associated phagocytosis)-engaged phagosomes

• no recruitment of Atg5-12 and Atg16l to LAP (LC3-associated phagocytosis)-engaged phagosomes

• lack of phosphatidylinositol 3-phosphate generation by Pick3c3 (VPS34) associated with LAP (LC3-associated phagocytosis)-engaged phagosomes

• failure to produce ROS (reactive oxygen species) upon zymosan stimulation

• lack of phosphorylated Ncf4 (p-p40PHOX) in LAP (LC3-associated phagocytosis)-engaged phagosomes

• levels of Cyba (p22PHOX) in LAP (LC3-associated phagocytosis)-engaged phagosomes

mortality/aging

mortality/aging ( J:261225 )

N • mice are born at expected Mendelian ratios

Genotype
MGI:6287978

hm2

• Allelic Composition: Rubcn^em1Dgre/Rubcn^em1Dgre
• Genetic Background: involves: C57BL/6 * C57BL/6N

growth/size/body

decreased body weight ( J:235399 )

• mice appear normal at weaning but fail to gain weight

hematopoietic system

increased neutrophil cell number ( J:235399 )

• increase in levels of circulating neutrophils

increased lymphocyte cell number ( J:235399 )

• increase in levels of circulating lymphocytes

increased CD8-positive, alpha-beta T cell number ( J:235399 )

• increase in circulating activated CD8+ T cells

increased monocyte cell number ( J:235399 )

• increase in levels of circulating monocytes

abnormal spleen morphology ( J:235399 )

• spleens show increased expression of interfron signature genes such as Ddx58 and Isg95

increased IgG level ( J:235399 )

• IgG deposition in the glomeruli of kidneys

abnormal macrophage physiology ( J:235399 )

• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages

• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity

homeostasis/metabolism

increased circulating creatinine level ( J:235399 )

increased blood urea nitrogen level ( J:235399 )

abnormal circulating chemokine level ( J:235399 )

• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice

increased circulating interleukin-1 beta level ( J:235399 )

• in 52-week old mice

decreased circulating interleukin-10 level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-12b level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-6 level ( J:235399 )

• in 52-week old mice

increased urine protein level ( J:235399 )

immune system

increased neutrophil cell number ( J:235399 )

• increase in levels of circulating neutrophils

increased lymphocyte cell number ( J:235399 )

• increase in levels of circulating lymphocytes

increased CD8-positive, alpha-beta T cell number ( J:235399 )

• increase in circulating activated CD8+ T cells

increased monocyte cell number ( J:235399 )

• increase in levels of circulating monocytes

abnormal spleen morphology ( J:235399 )

• spleens show increased expression of interfron signature genes such as Ddx58 and Isg95

increased IgG level ( J:235399 )

• IgG deposition in the glomeruli of kidneys

abnormal macrophage physiology ( J:235399 )

• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages

• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity

abnormal circulating chemokine level ( J:235399 )

• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice

increased circulating interleukin-1 beta level ( J:235399 )

• in 52-week old mice

decreased circulating interleukin-10 level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-12b level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-6 level ( J:235399 )

• in 52-week old mice

increased susceptibility to systemic lupus erythematosus ( J:235399 )

• mice develop a systemic lupus erythematosus-like disease (SLE)

• repeated injection of dying UV-irradiated thymocytes in mice accelerates the development of SLE-like disease, including increased serum levels of autoantibodies, glomerular immune complex deposition, and increased levels of alanine aminotransferase indicative of tissue damage

increased autoantibody level ( J:235399 )

• increase in serum levels of a broad array of antibodies against autoantigens commonly associated with SLE

increased anti-nuclear antigen antibody level ( J:235399 )

• increase in serum levels of anti-nuclear antibodies

• mice injected with UV-irradiated thymocytes beginning at 6 weeks of age over an 8 week period show a significant increase in serum levels of ANA and anti-dsDNA antibodies compared to wild-type mice which show minimal increases

increased anti-double stranded DNA antibody level ( J:235399 )

• increase in serum levels of anti-double-stranded DNA antibodies

• mice injected with UV-irradiated thymocytes beginning at 6 weeks of age over an 8 week period show a significant increase in serum levels of ANA and anti-dsDNA antibodies compared to wild-type mice which show minimal increases

glomerulonephritis ( J:235399 )

• kidneys from aged mice show endocapillary proliferative glomerulonephritis

renal/urinary system

increased urine protein level ( J:235399 )

abnormal kidney morphology ( J:235399 )

• mice show indications of kidney damage and show increased functional markers of kidney injury

abnormal renal glomerulus morphology ( J:235399 )

• IgG and complement C1q deposition in the glomeruli of kidneys

glomerulonephritis ( J:235399 )

• kidneys from aged mice show endocapillary proliferative glomerulonephritis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:235399

Genotype
MGI:6196878

cx3

• Allelic Composition: Rubcn^em1Dgre/Rubcn^em1Dgre; Tg(CAG-EGFP/Map1lc3b)53Nmz/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N * C57BL/6NCrlj * DBA/2

hematopoietic system

abnormal macrophage morphology ( J:261225 )

• increased numbers of LC3 (Map1lc3) puncta

abnormal macrophage physiology ( J:261225 )

• unable to translocate LC3 (Map1lc3) to LAP (LC3-associated phagocytosis)-engaged phagosome

• phagocytosis

immune system

abnormal macrophage morphology ( J:261225 )

• increased numbers of LC3 (Map1lc3) puncta

abnormal macrophage physiology ( J:261225 )

• unable to translocate LC3 (Map1lc3) to LAP (LC3-associated phagocytosis)-engaged phagosome

• phagocytosis

Genotype
MGI:6287979

cx4

• Allelic Composition: Rubcn^em1Dgre/Rubcn^em1Dgre; Tg(CAG-EGFP/Map1lc3b)53Nmz/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * DBA/2

hematopoietic system

abnormal macrophage physiology ( J:235399 )

• mice injected with UV-irradiated dying thymocytes into the spleen, liver, or kidney exhibit defective clearance of engulfed, dying cells and no induction of LC3-II, indicating failure of LC3-associated phagocytosis-dependent mechanism to degrade engulfed corpses

homeostasis/metabolism

abnormal circulating chemokine level ( J:235399 )

• serum CCL4 levels are acutely increased in mice injected with UV-irradiated dying thymocytes

increased circulating interleukin-1 beta level ( J:235399 )

• serum IL-1beta levels are acutely increased in mice injected with UV-irradiated dying thymocytes

decreased circulating interleukin-10 level ( J:235399 )

• serum IL-10 levels are not increased in mutant mice injected with UV-irradiated dying thymocytes like in wild-type mice

increased circulating interleukin-6 level ( J:235399 )

• serum IL-6 levels are acutely increased in mice injected with UV-irradiated dying thymocytes

immune system

abnormal macrophage physiology ( J:235399 )

• mice injected with UV-irradiated dying thymocytes into the spleen, liver, or kidney exhibit defective clearance of engulfed, dying cells and no induction of LC3-II, indicating failure of LC3-associated phagocytosis-dependent mechanism to degrade engulfed corpses

abnormal circulating chemokine level ( J:235399 )

• serum CCL4 levels are acutely increased in mice injected with UV-irradiated dying thymocytes

increased circulating interleukin-1 beta level ( J:235399 )

• serum IL-1beta levels are acutely increased in mice injected with UV-irradiated dying thymocytes

decreased circulating interleukin-10 level ( J:235399 )

• serum IL-10 levels are not increased in mutant mice injected with UV-irradiated dying thymocytes like in wild-type mice

increased circulating interleukin-6 level ( J:235399 )

• serum IL-6 levels are acutely increased in mice injected with UV-irradiated dying thymocytes