Phenotypes Associated with This Genotype

Genotype
MGI:3769143

• Allelic Composition: Fas^lpr/Fas^lpr; Irf1^tm1Mak/Irf1^tm1Mak
• Genetic Background: MRL.Cg-Irf1^tm1Mak Fas^lpr

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

mortality/aging

premature death ( J:114771 )

• 50% of mice die by 45 weeks; survival is increased relative to MRL-Fas^lpr mice

immune system

immune system phenotype ( J:114771 )

N • TNF alpha production is not significantly different from Fas^lpr, Irf1-sufficient mice

increased CD4-positive, alpha-beta T cell number ( J:114771 )

• at 12 weeks, splenic CD4+CD25+ T cells are increased in percentage compared to wild-type MRL-Fas^lpr mice; percentage increases from 27.1% at 8 weeks to 40.3% at 26 weeks in wild-type mice, double mutants have 60.6% at 26 weeks

• 26 week old mice have a percentage of CD4+CD25+CD62L+ T cells (32.2%) compared to wild-type MRL-Fas^lpr mice (13.1%)

abnormal cytokine secretion ( J:114771 )

• mesangial cells from 8- and 26-week old mice show significantly less Il12 production than Fas^lpr, Irf1-sufficient cells upon stimulation with LPS and interferon gamma

decreased anti-double stranded DNA antibody level ( J:114771 )

• levels of anti-dsDNA IgG2a are significantly decreased relative to Fas^lpr, Irf1-sufficient mice

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show much less severe renal disease including IgG and C3 glomerular deposition compared to Fas^lpr homozygotes

hematopoietic system

increased CD4-positive, alpha-beta T cell number ( J:114771 )

• at 12 weeks, splenic CD4+CD25+ T cells are increased in percentage compared to wild-type MRL-Fas^lpr mice; percentage increases from 27.1% at 8 weeks to 40.3% at 26 weeks in wild-type mice, double mutants have 60.6% at 26 weeks

• 26 week old mice have a percentage of CD4+CD25+CD62L+ T cells (32.2%) compared to wild-type MRL-Fas^lpr mice (13.1%)

renal/urinary system

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show much less severe renal disease including IgG and C3 glomerular deposition compared to Fas^lpr homozygotes

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:114771 )

N • only 1 mouse had abnormal urine protein levels (above 200 mg/dl) at 24 weeks of age

cellular

abnormal cell physiology ( J:114771 )

• in response to LPS + IFN gamma stimulation, mesangial cells show significantly lower activation than cells from MRL-Fas^lpr mice

integument

integument phenotype ( J:114771 )

N • mice do not show characteristic signs of skin disease; at 26 weeks of age, 7/10 mice show no skin involvement, while 3 show minimal skin irritation, compared to 8/10 Fas^lpr, Irf1 sufficient mice displaying moderate to severe skin involvement