Phenotypes Associated with This Genotype

Genotype
MGI:5478500

• Allelic Composition: Fas^lpr/Fas^lpr; Tlr9^tm1Aki/Tlr9^tm1Aki
• Genetic Background: MRL.Cg-Tlr9^tm1Aki Fas^lpr

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

mortality/aging

premature death ( J:113557 )

• mutants show accelerated mortality relative to Fas^lpr homozygotes, with a median survival of 16.4 weeks compared to 25.1 weeks for Fas^lpr homozygotes

immune system

enlarged spleen ( J:113557 )

• splenomegaly is increased more than in Fas^lpr homozygotes

increased double-negative T cell number ( J:113557 )

• 3-fold increase in the number of CD4- CD8- double-negative T cells in the spleen compared to Fas^lpr homozygotes

increased CD4-positive, alpha-beta T cell number ( J:113557 )

• increase in number of CD4+ helper T cells compared to Fas^lpr homozygotes

abnormal B cell activation ( J:113557 )

• B cells have increased expression of activation markers CD44 and CD69 compared to Fas^lpr homozygotes, indicating increased B cell activation

increased IgG level ( J:113557 )

• increase in concentration of every IgG isotype compared to Fas^lpr homozygotes, with most prominent increases in IgG2a and IgG3

increased IgG2a level ( J:113557 )

• compared to Fas^lpr homozygotes

increased IgG3 level ( J:113557 )

• compared to Fas^lpr homozygotes

increased circulating interferon-alpha level ( J:113557 )

• mice exhibit increased serum IFN-alpha concentration compared to Fas^lpr homozygotes

enlarged lymph nodes ( J:113557 )

• lymphadenopathy is increased more than in Fas^lpr homozygotes

abnormal plasmacytoid dendritic cell physiology ( J:113557 )

• splenic plasmacytoid dendritic cells (pDC) are more activated than those in single Fas^lpr homozygotes based on increased expression of MHC class II

• plasmacytoid DCs have an increased expression of the activation markers CD80 and CD86 compared to Fas^lpr homozygotes

increased susceptibility to systemic lupus erythematosus ( J:113557 )

• mutants exhibit an increase in the incidence and severity of autoimmune skin disease compared to single Fas^lpr homozygous littermates

• mutants develop exacerbated kidney disease (lupus nephritis) compared to single Fas^lpr homozygotes

decreased autoantibody level ( J:113557 )

• mutants show impaired ability to generate antibodies to DNA antigens compared to single Fas^lpr homozygotes, however they do generate antibodies reacting with cytoplasmic antigens that may include RNA

increased autoantibody level ( J:113557 )

• mice exhibit an elevated baseline level of anti-Smith-ribonucleoprotein autoantibodies compared to single Fas^lpr homozygotes

kidney inflammation ( J:113557 )

• mutants develop exacerbated kidney disease (lupus nephritis) compared to Fas^lpr homozygotes

• a trend towards increased severity of interstitial infiltrates compared to Fas^lpr homozygotes

glomerulonephritis ( J:113557 )

• increase in glomerular size, cellularity, and protein deposition in kidneys leading to glomerulonephritis

renal/urinary system

kidney inflammation ( J:113557 )

• mutants develop exacerbated kidney disease (lupus nephritis) compared to Fas^lpr homozygotes

• a trend towards increased severity of interstitial infiltrates compared to Fas^lpr homozygotes

glomerulonephritis ( J:113557 )

• increase in glomerular size, cellularity, and protein deposition in kidneys leading to glomerulonephritis

abnormal renal glomerulus morphology ( J:113557 )

• glomerular size and cellularity are increased compared to Fas^lpr homozygotes

hematopoietic system

enlarged spleen ( J:113557 )

• splenomegaly is increased more than in Fas^lpr homozygotes

increased double-negative T cell number ( J:113557 )

• 3-fold increase in the number of CD4- CD8- double-negative T cells in the spleen compared to Fas^lpr homozygotes

increased CD4-positive, alpha-beta T cell number ( J:113557 )

• increase in number of CD4+ helper T cells compared to Fas^lpr homozygotes

abnormal B cell activation ( J:113557 )

• B cells have increased expression of activation markers CD44 and CD69 compared to Fas^lpr homozygotes, indicating increased B cell activation

increased IgG level ( J:113557 )

• increase in concentration of every IgG isotype compared to Fas^lpr homozygotes, with most prominent increases in IgG2a and IgG3

increased IgG2a level ( J:113557 )

• compared to Fas^lpr homozygotes

increased IgG3 level ( J:113557 )

• compared to Fas^lpr homozygotes

homeostasis/metabolism

increased circulating interferon-alpha level ( J:113557 )

• mice exhibit increased serum IFN-alpha concentration compared to Fas^lpr homozygotes

growth/size/body

enlarged spleen ( J:113557 )

• splenomegaly is increased more than in Fas^lpr homozygotes

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:113557