Phenotypes Associated with This Genotype

Genotype
MGI:7284986

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

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

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