Phenotypes Associated with This Genotype

Genotype
MGI:7284974

• Allelic Composition: Tlr7^em2Anu/Tlr7⁺
• 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 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