Mouse Genome Informatics
hm
    Faslpr/Faslpr
MRL/MpJ-Faslpr/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• 50% mortality is observed at 5 months with 90% mortality at 7.5 months, significantly reduced from wild-type

immune system
• mild to moderated neutrophil accumulation is observed at 20 weeks
• CD19+IgM+ immature B cells are reduced in the spleen
• numbers of the T1 subset of B cells is reduced
• CD19+ IgDhigh IgMlow B cells are severely reduced in the spleen
• numbers of marginal zone (MZ) B cells is reduced
• increased B220+IgM+ cells are observed in bone marrow; number of IgG-secreting cells are significantly increased compared to Faslpr homozygotes
• staining intensity and number of germinal centers (GCs) is reduced 10 days post-challenge with NP-KLH antigen, compared to controls
• in vitro, splenic B cells produce significantly higher amounts of IgG1 in response to LPS and anti-CD40 plus Il4 stimulation, and higher amounts of IgG2a upon LPS stimulation
• production of anti-NP IgG is impaired in spleen cells
• IgG and IgM levels are increased in serum at 6 months (J:7454)
• mice display hypergammaglobulinemia; serum levels are comparable to Fas homozygotes (J:122315)
• mice exhibit increased serum IgG levels and IgG deposits in the kidney unlike wild-type mice
• larger lymph nodes often show extensive hemorrhage and necrosis
• nodes are 62 times normal size (J:7454)
• mice exhibit increased serum levels of kappa-chain rheumatoid factor and DNA auto-antibodies, lymphadenopathy, glomerulonephritis, renal immunoglobulin deposits, proteinuria, and end organ disease compared to in wild-type mice
• at 16 weeks, levels of anti-cardiolipin antibodies are significantly higher than in wild-type controls; levels are significantly higher at 8 weeks (J:14151)
• mice exhibit increased serum levels of kappa-chain rheumatoid factor compared to in wild-type mice (J:92084)
• mice have significantly increased levels of anti-ssDNA antibodies (J:7454)
• at 16 weeks, anti-DNA titers are significantly higher than in wild-type controls (J:14151)
• DNA auto-antibodies are increased compared to in wild-type mice at 12 weeks (J:92084)
• by 5-6 months of age, Fas-deficient mice have antinuclear antibody (ANA) levels comparable to >50% of C4b-deficient females (on Ighb haplotype homozygous background) (J:111811)
• antibodies are increased relative to controls and other mutant strains with Faslpr mutations (J:7454)
• mice produce high titers of IgG1 and IgG2a anti-dsDNA antibodies, comparable to Fas homozygotes (J:122315)
• at 20 weeks, all mice show mononuclear infiltrates in the choroid plexus; at 10 weeks, all mice display monuclear infiltrates
• Background Sensitivity: severe immune complex glomerulonephritis develops by 6 months (J:7454)
• mice show deposition of IgG or C3 in kidneys and inflammation, similar to Fas homozygotes (J:122315)
• kidney lesions have lower scores than those in double mutants at 20 weeks (J:127199)

hematopoietic system
• mild to moderated neutrophil accumulation is observed at 20 weeks
• CD19+IgM+ immature B cells are reduced in the spleen
• numbers of the T1 subset of B cells is reduced
• CD19+ IgDhigh IgMlow B cells are severely reduced in the spleen
• numbers of marginal zone (MZ) B cells is reduced
• increased B220+IgM+ cells are observed in bone marrow; number of IgG-secreting cells are significantly increased compared to Faslpr homozygotes
• staining intensity and number of germinal centers (GCs) is reduced 10 days post-challenge with NP-KLH antigen, compared to controls
• in vitro, splenic B cells produce significantly higher amounts of IgG1 in response to LPS and anti-CD40 plus Il4 stimulation, and higher amounts of IgG2a upon LPS stimulation
• production of anti-NP IgG is impaired in spleen cells
• IgG and IgM levels are increased in serum at 6 months (J:7454)
• mice display hypergammaglobulinemia; serum levels are comparable to Fas homozygotes (J:122315)
• mice exhibit increased serum IgG levels and IgG deposits in the kidney unlike wild-type mice

renal/urinary system
• mice have excessive urinary albumin compared to wild-type (>10-fold) at 3-4 months
• foot processes are only focally effaced
• dilated capsules are observed in mice at 3-4 months
• abnormalities due to severe glomerulonephritis (J:7454)
• at 20 weeks, lesions show some neutrophil infiltration and hypercellularity (J:127199)
• tuft necrosis, capsular proliferation and fibrosis are less common and less severe than observed in double mutants (J:127199)
• mild increase in mesangial cells is seen at 20 weeks of age
• mild increase in mesangial matrix is seen at 20 weeks of age
• glomerulonephritic changes such as hypercellularity, lobularity, dilated capsules and crescent formation or enlarged glomeruli are observed in mice at 3-4 months
• Background Sensitivity: severe immune complex glomerulonephritis develops by 6 months (J:7454)
• mice show deposition of IgG or C3 in kidneys and inflammation, similar to Fas homozygotes (J:122315)
• kidney lesions have lower scores than those in double mutants at 20 weeks (J:127199)
• crescent formation is observed in mice at 3-4 months
• enlarged glomeruli are observed in mice at 3-4 months
• progressive decline in renal function is observed, during progression to end-stage renal disease

behavior/neurological
• mice show increased latency to locate hidden platform in water maze testing on days 2-5 of testing at 8 weeks of age; at 16 weeks in spatial bias testing, mutants spend less time and travel reduced distances in quadrant of platform's previous location compared to controls
• equilibrium is significantly impaired in mice at 18-20 weeks, as measured by performance in rotarod tests

vision/eye

cardiovascular system
• myocardium neighboring the heart valves shows mononuclear infiltration of the vessels, but valves are normal

hearing/vestibular/ear
• slight degenerative changes in the stria vascularis of both the apical and basal turns
• the basement membrane of the capillaries in the stria vascularis was thickened
• widened intercellular space in the stria vascularis
• the basal infolding of strial marginal cells
• thinned intermediate cell layer
• the ABR threshold f the 20-week-old mutant mice were significantly higher than those of the 4-week-old mutant mice and the 20-week-old wild-type BALB/c mice

nervous system
• at 20 weeks, all mice show mononuclear infiltrates in the choroid plexus; at 10 weeks, all mice display monuclear infiltrates

homeostasis/metabolism
• mice have excessive urinary albumin compared to wild-type (>10-fold) at 3-4 months
• Background Sensitivity: 7-8 week old mice show 2-3 fold induction of Dnase1l3 in macrophages and 4-5 fold induction in splenocytes over C57BL/6; levels in other strains like BXSB/MpJ and (NZB x NZW)F1 are similarly elevated compared to B6
• Background Sensitivity: mice show a dramatic defect (~8-fold decrease) in macrophage-secreted Dnase1l3 barrier to liposomal (BT) activity compared to B6; (NZB x NZW)F1 mice show a similar defect in BT activity

pigmentation
• thinned intermediate cell layer

digestive/alimentary system

endocrine/exocrine glands

Mouse Models of Human Disease
OMIM IDRef(s)
Sjogren Syndrome 270150 J:123192