Phenotypes associated with this allele

• Allele Symbol: Tlr7^em2Anu
• Allele Name: endonuclease-mediated mutation 2, Australian National University
• Allele ID: MGI:7279260
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tlr7^em2Anu/Tlr7^em2Anu	C57BL/6NCrl-Tlr7^em2Anu	MGI:7284944
ht2	Tlr7^em2Anu/Tlr7^+	C57BL/6NCrl-Tlr7^em2Anu	MGI:7284974
cx3	Rnaseh2b^em1Anu/Rnaseh2b^+ Tlr7^em2Anu/Tlr7^+	C57BL/6NCrl-Rnaseh2b^em1Anu Tlr7^em2Anu	MGI:7284994
ot4	Tlr7^em2Anu/Y	C57BL/6NCrl-Tlr7^em2Anu	MGI:7284986

Genotype
MGI:7284944

hm1

• Allelic Composition: Tlr7^em2Anu/Tlr7^em2Anu
• Genetic Background: C57BL/6NCrl-Tlr7^em2Anu

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

mortality/aging

premature death ( J:324448 )

♀ • mice show decreased survival

growth/size/body

enlarged spleen ( J:324448 )

♀ • splenomegaly with increased cellularity is seen in 12-week-old mice

spleen hyperplasia ( J:324448 )

♀ • 12-week-old mice show increased spleen cellularity

immune system

enlarged spleen ( J:324448 )

♀ • splenomegaly with increased cellularity is seen in 12-week-old mice

spleen hyperplasia ( J:324448 )

♀ • 12-week-old mice show increased spleen cellularity

increased B cell number ( J:324448 )

♀ • spleen shows reduced T:B cell ratio with an increase in in total B cells

increased plasma cell number ( J:324448 )

♀ • spleen shows an increase in plasma cells

increased CD4-positive, alpha-beta T cell number ( J:324448 )

♀ • CXCR3+ extrafollicular helper CD4+ T cells are increased

increased effector memory CD4-positive, alpha-beta T cell number ( J:324448 )

♀ • effector or memory CD4+CD44high cells are increased

increased T follicular helper cell number ( J:324448 )

♀

decreased leukocyte cell number ( J:324448 )

♀ • slightly lower white blood cell count

abnormal mature B cell morphology ( J:324448 )

♀ • spleen shows an increase in age-associated B cells (B220+CD21-CXCR5-CD19hiCD11c+)

♀ • age-associated B cells are also expanded in the blood and kidneys

increased germinal center B cell number ( J:324448 )

♀ • increase in germinal center B cells (CD19+CD95+BCL6+)

decreased marginal zone B cell number ( J:324448 )

♀ • percentage of splenic marginal zone B cells is decreased, but the total numbers are not decreased

increased spleen germinal center number ( J:324448 )

♀ • spleen shows spontaneous germinal centers

abnormal Peyer's patch morphology ( J:324448 )

♀ • hyperplasia of Peyer's patches

abnormal plasmacytoid dendritic cell physiology ( J:324448 )

♀ • plasmacytoid dendritic cells appear to be activated with increased MHC-II and reduced siglec-H expression

increased susceptibility to systemic lupus erythematosus ( J:324448 )

♀

increased anti-nuclear antigen antibody level ( J:324448 )

♀ • ANAs are detected from 6 weeks of age in females

increased anti-single stranded DNA antibody level ( J:324448 )

♀ • mice show increased autoantibodies to ssDNA at 6 weeks but not 4 weeks of age

increased inflammatory response ( J:324448 )

♀

salivary gland inflammation ( J:324448 )

♀ • lymphoid infiltrates in the salivary glands

pancreas inflammation ( J:324448 )

♀ • lymphoid infiltrates in the pancreas where they occasionally form peri-islet follicular structures

lymph node inflammation ( J:324448 )

♀ • chronic lymphadenitis of the regional, mesenteric, and inguinal lymph nodes including those in the gut, salivary glands, lungs

liver inflammation ( J:324448 )

♀ • lymphoid infiltrates in the liver

glomerulonephritis ( J:324448 )

♀ • proliferative glomerulonephritis

lung inflammation ( J:324448 )

♀ • subpleural, perivascular and interstitial lymphocytic and mononuclear cell infiltrates in the lungs

cardiovascular system

cardiac fibrosis ( J:324448 )

♀ • focal myocardial fibrosis

digestive/alimentary system

abnormal exocrine pancreas morphology ( J:324448 )

♀ • exocrine pancreatic tissue is often replaced with fat

salivary gland inflammation ( J:324448 )

♀ • lymphoid infiltrates in the salivary glands

endocrine/exocrine glands

abnormal exocrine pancreas morphology ( J:324448 )

♀ • exocrine pancreatic tissue is often replaced with fat

salivary gland inflammation ( J:324448 )

♀ • lymphoid infiltrates in the salivary glands

pancreas inflammation ( J:324448 )

♀ • lymphoid infiltrates in the pancreas where they occasionally form peri-islet follicular structures

hematopoietic system

enlarged spleen ( J:324448 )

♀ • splenomegaly with increased cellularity is seen in 12-week-old mice

spleen hyperplasia ( J:324448 )

♀ • 12-week-old mice show increased spleen cellularity

increased B cell number ( J:324448 )

♀ • spleen shows reduced T:B cell ratio with an increase in in total B cells

increased germinal center B cell number ( J:324448 )

♀ • increase in germinal center B cells (CD19+CD95+BCL6+)

increased plasma cell number ( J:324448 )

♀ • spleen shows an increase in plasma cells

increased CD4-positive, alpha-beta T cell number ( J:324448 )

♀ • CXCR3+ extrafollicular helper CD4+ T cells are increased

increased effector memory CD4-positive, alpha-beta T cell number ( J:324448 )

♀ • effector or memory CD4+CD44high cells are increased

increased T follicular helper cell number ( J:324448 )

♀

decreased leukocyte cell number ( J:324448 )

♀ • slightly lower white blood cell count

abnormal mature B cell morphology ( J:324448 )

♀ • spleen shows an increase in age-associated B cells (B220+CD21-CXCR5-CD19hiCD11c+)

♀ • age-associated B cells are also expanded in the blood and kidneys

decreased marginal zone B cell number ( J:324448 )

♀ • percentage of splenic marginal zone B cells is decreased, but the total numbers are not decreased

increased spleen germinal center number ( J:324448 )

♀ • spleen shows spontaneous germinal centers

liver/biliary system

liver inflammation ( J:324448 )

♀ • lymphoid infiltrates in the liver

muscle

abnormal muscle morphology ( J:324448 )

♀ • myocyte degeneration and necrosis in skin panniculus muscle

neoplasm

increased splenic marginal zone lymphoma incidence ( J:324448 )

♀ • splenic lymphomas

renal/urinary system

glomerulonephritis ( J:324448 )

♀ • proliferative glomerulonephritis

respiratory system

lung inflammation ( J:324448 )

♀ • subpleural, perivascular and interstitial lymphocytic and mononuclear cell infiltrates in the lungs

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:324448

Genotype
MGI:7284974

ht2

• Allelic Composition: Tlr7^em2Anu/Tlr7⁺
• Genetic Background: C57BL/6NCrl-Tlr7^em2Anu

mortality/aging

premature death ( J:324448 )

♀ • mice show decreased survival

growth/size/body

enlarged spleen ( J:324448 )

♀ • splenomegaly with increased cellularity is seen in 12-week-old mice

spleen hyperplasia ( J:324448 )

♀ • 12-week-old mice show increased spleen cellularity

immune system

enlarged spleen ( J:324448 )

♀ • splenomegaly with increased cellularity is seen in 12-week-old mice

spleen hyperplasia ( J:324448 )

♀ • 12-week-old mice show increased spleen cellularity

increased B cell number ( J:324448 )

♀ • spleen shows reduced T:B cell ratio with an increase in in total B cells

increased plasma cell number ( J:324448 )

♀ • spleen shows an increase in plasma cells

increased CD4-positive, alpha-beta T cell number ( J:324448 )

♀ • CXCR3+ extrafollicular helper CD4+ T cells are increased

increased T follicular helper cell number ( J:324448 )

♀

abnormal mature B cell morphology ( J:324448 )

♀ • spleen shows an increase in age-associated B cells (B220+CD21-CXCR5-CD19hiCD11c+)

♀ • age-associated B cells are also expanded in the blood and kidneys

increased germinal center B cell number ( J:324448 )

♀ • increase in germinal center B cells (CD19+CD95+BCL6+)

decreased marginal zone B cell number ( J:324448 )

♀ • percentage of splenic marginal zone B cells is decreased, but the total numbers are not decreased

increased spleen germinal center number ( J:324448 )

♀ • spleen shows spontaneous germinal centers

increased circulating interferon-gamma level ( J:324448 )

♀

increased circulating interleukin-10 level ( J:324448 )

♀

increased circulating interleukin-6 level ( J:324448 )

♀

increased circulating tumor necrosis factor level ( J:324448 )

♀

abnormal plasmacytoid dendritic cell physiology ( J:324448 )

♀ • plasmacytoid dendritic cells appear to be activated with increased MHC-II and reduced siglec-H expression

increased autoantibody level ( J:324448 )

♀ • mice develop antibodies to the TLR7 ligands ssRNA and Smith protein and ribonucleoprotein (RNP)

increased anti-nuclear antigen antibody level ( J:324448 )

♀ • ANAs are detected from 6 weeks of age in females

increased anti-double stranded DNA antibody level ( J:324448 )

♀ • 60% of mice at 6 months of age show dsDNA antibodies compared to 20% of controls

increased anti-single stranded DNA antibody level ( J:324448 )

♀ • mice show increased autoantibodies to ssDNA at 6 weeks but not 4 weeks of age

hematopoietic system

enlarged spleen ( J:324448 )

♀ • splenomegaly with increased cellularity is seen in 12-week-old mice

spleen hyperplasia ( J:324448 )

♀ • 12-week-old mice show increased spleen cellularity

thrombocytopenia ( J:324448 )

♀

increased B cell number ( J:324448 )

♀ • spleen shows reduced T:B cell ratio with an increase in in total B cells

increased germinal center B cell number ( J:324448 )

♀ • increase in germinal center B cells (CD19+CD95+BCL6+)

increased plasma cell number ( J:324448 )

♀ • spleen shows an increase in plasma cells

increased CD4-positive, alpha-beta T cell number ( J:324448 )

♀ • CXCR3+ extrafollicular helper CD4+ T cells are increased

increased T follicular helper cell number ( J:324448 )

♀

abnormal mature B cell morphology ( J:324448 )

♀ • spleen shows an increase in age-associated B cells (B220+CD21-CXCR5-CD19hiCD11c+)

♀ • age-associated B cells are also expanded in the blood and kidneys

decreased marginal zone B cell number ( J:324448 )

♀ • percentage of splenic marginal zone B cells is decreased, but the total numbers are not decreased

increased spleen germinal center number ( J:324448 )

♀ • spleen shows spontaneous germinal centers

homeostasis/metabolism

increased circulating interferon-gamma level ( J:324448 )

♀

increased circulating interleukin-10 level ( J:324448 )

♀

increased circulating interleukin-6 level ( J:324448 )

♀

increased circulating tumor necrosis factor level ( J:324448 )

♀

renal/urinary system

expanded mesangial matrix ( J:324448 )

♀ • expanded mesangial matrix with electron-dense deposits and increased mesangial cellularity

renal glomerular immunoglobulin deposits ( J:324448 )

♀ • immunoglobulin deposits in the kidneys

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:324448

Genotype
MGI:7284994

cx3

• Allelic Composition: Rnaseh2b^em1Anu/Rnaseh2b⁺; Tlr7^em2Anu/Tlr7⁺
• Genetic Background: C57BL/6NCrl-Rnaseh2b^em1Anu Tlr7^em2Anu

immune system

abnormal immune system morphology ( J:324448 )

♀ • mice show a similar phenotype seen in female heterozygous Tlr7^em2Anu mice with no exacerbation of the cellular or serological phenotypes seen in these mice except for a mild enhancement in the expression of type I IFN signature genes

increased plasma cell number ( J:324448 )

♀ • spleen shows an increase in plasma cells

increased CD4-positive, alpha-beta T cell number ( J:324448 )

♀ • CXCR3+ extrafollicular helper CD4+ T cells are increased

increased T follicular helper cell number ( J:324448 )

♀

abnormal mature B cell morphology ( J:324448 )

♀ • spleen shows an increase in age-associated B cells (B220+CD21-CXCR5-CD19hiCD11c+)

♀ • age-associated B cells are also expanded in the blood and kidneys

increased germinal center B cell number ( J:324448 )

♀ • increase in germinal center B cells (CD19+CD95+BCL6+)

increased autoantibody level ( J:324448 )

♀ • mice develop autoantibodies to the TLR7 ligands ssRNA and Smith protein ribonucleoprotein (RNP) and DNA

hematopoietic system

increased plasma cell number ( J:324448 )

♀ • spleen shows an increase in plasma cells

increased CD4-positive, alpha-beta T cell number ( J:324448 )

♀ • CXCR3+ extrafollicular helper CD4+ T cells are increased

increased T follicular helper cell number ( J:324448 )

♀

abnormal mature B cell morphology ( J:324448 )

♀ • spleen shows an increase in age-associated B cells (B220+CD21-CXCR5-CD19hiCD11c+)

♀ • age-associated B cells are also expanded in the blood and kidneys

increased germinal center B cell number ( J:324448 )

♀ • increase in germinal center B cells (CD19+CD95+BCL6+)

Genotype
MGI:7284986

ot4

• Allelic Composition: Tlr7^em2Anu/Y
• Genetic Background: C57BL/6NCrl-Tlr7^em2Anu

mortality/aging

premature death ( J:324448 )

♂ • mice exhibit decreased survival

growth/size/body

enlarged spleen ( J:324448 )

♂ • splenomegaly with increased cellularity is seen in 12-week-old mice

immune system

enlarged spleen ( J:324448 )

♂ • splenomegaly with increased cellularity is seen in 12-week-old mice

increased CD4-positive, alpha-beta T cell number ( J:324448 )

♂ • CXCR3+ extrafollicular helper CD4+ T cells are increased

increased effector memory CD4-positive, alpha-beta T cell number ( J:324448 )

♂ • effector or memory CD4+CD44high cells are increased

increased T follicular helper cell number ( J:324448 )

♂

abnormal B cell physiology ( J:324448 )

♂ • total splenic B cells or CD93+B220low immature bone marrow cells activated with anti-IgM show enhanced survival compared to controls

decreased B cell apoptosis ( J:324448 )

♂ • mice show a decrease in tendency for apoptosis in age-associated B cells with decreased expression of active caspase-3

decreased B cell proliferation ( J:324448 )

♂ • mice show a small decrease in proliferation of age-associated B cells

abnormal macrophage physiology ( J:324448 )

♂ • bone-marrow derived macrophages show increased responsiveness to guanosine, producing higher levels of TNF

increased circulating interferon-gamma level ( J:324448 )

♂

increased circulating interleukin-10 level ( J:324448 )

♂

increased circulating interleukin-6 level ( J:324448 )

♂

increased circulating tumor necrosis factor level ( J:324448 )

♂

abnormal Peyer's patch morphology ( J:324448 )

♂ • hyperplasia of Peyer's patches

lymph node inflammation ( J:324448 )

♂ • chronic lymphadenitis of the regional, mesenteric, and inguinal lymph nodes including those in the gut, salivary glands, lungs

increased susceptibility to systemic lupus erythematosus ( J:324448 )

♂

increased autoantibody level ( J:324448 )

♂ • mice develop antibodies to the TLR7 ligands ssRNA and Smith protein ribonucleoprotein (RNP)

increased anti-nuclear antigen antibody level ( J:324448 )

♂

increased anti-double stranded DNA antibody level ( J:324448 )

♂ • 20% of mice at 6 months of age show dsDNA antibodies

increased anti-single stranded DNA antibody level ( J:324448 )

♂ • mice show increased autoantibodies to ssDNA at 6 weeks but not 4 weeks of age

liver inflammation ( J:324448 )

♂ • lymphoid infiltrates in the liver

lung inflammation ( J:324448 )

♂ • subpleural, perivascular and interstitial lymphocytic and mononuclear cell infiltrates in the lungs

cardiovascular system

cardiac fibrosis ( J:324448 )

♂ • focal myocardial fibrosis

cellular

decreased B cell apoptosis ( J:324448 )

♂ • mice show a decrease in tendency for apoptosis in age-associated B cells with decreased expression of active caspase-3

decreased B cell proliferation ( J:324448 )

♂ • mice show a small decrease in proliferation of age-associated B cells

hematopoietic system

enlarged spleen ( J:324448 )

♂ • splenomegaly with increased cellularity is seen in 12-week-old mice

increased CD4-positive, alpha-beta T cell number ( J:324448 )

♂ • CXCR3+ extrafollicular helper CD4+ T cells are increased

increased effector memory CD4-positive, alpha-beta T cell number ( J:324448 )

♂ • effector or memory CD4+CD44high cells are increased

increased T follicular helper cell number ( J:324448 )

♂

abnormal B cell physiology ( J:324448 )

♂ • total splenic B cells or CD93+B220low immature bone marrow cells activated with anti-IgM show enhanced survival compared to controls

decreased B cell apoptosis ( J:324448 )

♂ • mice show a decrease in tendency for apoptosis in age-associated B cells with decreased expression of active caspase-3

decreased B cell proliferation ( J:324448 )

♂ • mice show a small decrease in proliferation of age-associated B cells

abnormal macrophage physiology ( J:324448 )

♂ • bone-marrow derived macrophages show increased responsiveness to guanosine, producing higher levels of TNF

homeostasis/metabolism

increased circulating interferon-gamma level ( J:324448 )

♂

increased circulating interleukin-10 level ( J:324448 )

♂

increased circulating interleukin-6 level ( J:324448 )

♂

increased circulating tumor necrosis factor level ( J:324448 )

♂

liver/biliary system

liver inflammation ( J:324448 )

♂ • lymphoid infiltrates in the liver

muscle

abnormal muscle morphology ( J:324448 )

♂ • myocyte degeneration and necrosis in skin panniculus muscle

neoplasm

increased splenic marginal zone lymphoma incidence ( J:324448 )

♂ • splenic lymphomas

respiratory system

lung inflammation ( J:324448 )

♂ • subpleural, perivascular and interstitial lymphocytic and mononuclear cell infiltrates in the lungs

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:324448