Phenotypes Associated with This Genotype

Genotype
MGI:3798887

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: B6.MRL-Fas^lpr

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

mortality/aging

premature death ( J:135036 , J:6638 , J:7454 )

• 64% survival at 24 weeks (J:135036)

• median survival is 284 days, compared to 795 days for controls (J:6638)

• 50% mortality is observed at 13.5 months with 90% mortality at 16 months, significantly reduced from wild-type (J:7454)

immune system

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

enlarged spleen ( J:135036 )

increased double-negative T cell number ( J:135036 )

increased immunoglobulin level ( J:7454 )

• IgG and IgM levels are increased in serum at 6 months

enlarged lymph nodes ( J:135036 , J:6638 , J:7454 )

• generalized lymphadenopathy (J:135036)

• by 4 months of age, lymph nodes are increased 10- to 20-fold (J:6638)

• nodes are 13 times normal size (J:7454)

lymph node necrosis ( J:7454 )

• larger lymph nodes often show extensive necrosis

decreased interleukin-2 secretion ( J:6638 )

• defect in Il2 activity begins during early life and worsens with age; spleen cells show no stimulated Il2 production upon stimulation with concanavalin A

increased autoantibody level ( J:135036 , J:7454 )

• mice have elevated levels of anti-chromatin antibodies compared to double mutants (J:135036)

• increase in thymocytotoxic autoantibodies at 6 months is seen (J:7454)

increased anti-nuclear antigen antibody level ( J:135036 , J:6638 )

• mice have elevated levels of anti-chromatin (anti-nucleosome) antibodies compared to double mutants (J:135036)

• anti-nuclear antibodies are present at 6 months of age (J:6638)

increased anti-double stranded DNA antibody level ( J:7454 )

• antibodies are increased relative to controls

glomerulonephritis ( J:135036 , J:7454 )

• interstitial lymphoid infiltration is observed at 6 months; glomerular IgG deposits that are exclusively mesangial are observed (J:135036)

• Background Sensitivity: immune complex glomerulonephritis develops by 1 year of age but is much milder than in MRL homozygotes (J:7454)

renal/urinary system

abnormal renal glomerulus morphology ( J:7454 )

• nephritic changes consist of focal increase in mesangial substance and mild mesangial proliferation

increased mesangial cell number ( J:7454 )

• mild mesangial proliferation

glomerulonephritis ( J:135036 , J:7454 )

• interstitial lymphoid infiltration is observed at 6 months; glomerular IgG deposits that are exclusively mesangial are observed (J:135036)

• Background Sensitivity: immune complex glomerulonephritis develops by 1 year of age but is much milder than in MRL homozygotes (J:7454)

expanded mesangial matrix ( J:7454 )

• focal increase in mesangial substance

renal glomerular immunoglobulin deposits ( J:135036 , J:7454 )

hematopoietic system

enlarged spleen ( J:135036 )

increased double-negative T cell number ( J:135036 )

increased immunoglobulin level ( J:7454 )

• IgG and IgM levels are increased in serum at 6 months

cardiovascular system

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

cellular

increased mesangial cell number ( J:7454 )

• mild mesangial proliferation

growth/size/body

enlarged spleen ( J:135036 )