Phenotypes Associated with This Genotype

Genotype
MGI:3639605

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: MRL/MpJ-Fas^lpr/J

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

mortality/aging

premature death ( J:7454 )

• 50% mortality is observed at 5 months with 90% mortality at 7.5 months, significantly reduced from wild-type

cellular

increased mesangial cell number ( J:127199 )

• mild increase in mesangial cells is seen at 20 weeks of age

immune system

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

salivary gland inflammation ( J:92084 )

decreased immature B cell number ( J:122315 )

• CD19+IgM+ immature B cells are reduced in the spleen

decreased transitional stage B cell number ( J:122315 )

• numbers of the T1 subset of B cells is reduced

increased neutrophil cell number ( J:127199 )

• mild to moderated neutrophil accumulation is observed at 20 weeks

decreased mature B cell number ( J:122315 )

• CD19+ IgD^high IgM^low B cells are severely reduced in the spleen

decreased marginal zone B cell number ( J:122315 )

• numbers of marginal zone (MZ) B cells is reduced

increased plasma cell number ( J:122315 )

• increased B220+IgM+ cells are observed in bone marrow; number of IgG-secreting cells are significantly increased compared to Fas^lpr homozygotes

decreased spleen germinal center number ( J:122315 )

• staining intensity and number of germinal centers (GCs) is reduced 10 days post-challenge with NP-KLH antigen, compared to controls

abnormal immunoglobulin level ( J:122315 )

• 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

decreased IgG level ( J:122315 )

• production of anti-NP IgG is impaired in spleen cells

increased immunoglobulin level ( J:7454 , J:122315 )

• 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)

increased IgG level ( J:92084 )

• mice exhibit increased serum IgG levels and IgG deposits in the kidney unlike wild-type mice

enlarged lymph nodes ( J:7454 , J:92084 )

• nodes are 62 times normal size (J:7454)

lymph node necrosis ( J:7454 )

• larger lymph nodes often show extensive necrosis

increased susceptibility to systemic lupus erythematosus ( J:92084 )

• 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

increased autoantibody level ( J:14151 , J:92084 )

• 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)

increased anti-nuclear antigen antibody level ( J:7454 , J:14151 , J:92084 , J:111811 )

• 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 Igh^b haplotype homozygous background) (J:111811)

increased anti-double stranded DNA antibody level ( J:7454 , J:92084 , J:122315 )

• antibodies are increased relative to controls and other mutant strains with Fas^lpr mutations (J:7454)

• mice produce high titers of IgG1 and IgG2a anti-dsDNA antibodies, comparable to Fas homozygotes (J:122315)

CNS inflammation ( J:14151 )

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

conjunctivitis ( J:123192 )

glomerulonephritis ( J:7454 , J:92084 , J:122315 , J:127199 )

• 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)

muscle

abnormal myocardium layer morphology ( J:14151 )

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

hematopoietic system

decreased immature B cell number ( J:122315 )

• CD19+IgM+ immature B cells are reduced in the spleen

decreased transitional stage B cell number ( J:122315 )

• numbers of the T1 subset of B cells is reduced

increased neutrophil cell number ( J:127199 )

• mild to moderated neutrophil accumulation is observed at 20 weeks

decreased mature B cell number ( J:122315 )

• CD19+ IgD^high IgM^low B cells are severely reduced in the spleen

decreased marginal zone B cell number ( J:122315 )

• numbers of marginal zone (MZ) B cells is reduced

increased plasma cell number ( J:122315 )

• increased B220+IgM+ cells are observed in bone marrow; number of IgG-secreting cells are significantly increased compared to Fas^lpr homozygotes

decreased spleen germinal center number ( J:122315 )

• staining intensity and number of germinal centers (GCs) is reduced 10 days post-challenge with NP-KLH antigen, compared to controls

abnormal immunoglobulin level ( J:122315 )

• 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

decreased IgG level ( J:122315 )

• production of anti-NP IgG is impaired in spleen cells

increased immunoglobulin level ( J:7454 , J:122315 )

• 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)

increased IgG level ( J:92084 )

• mice exhibit increased serum IgG levels and IgG deposits in the kidney unlike wild-type mice

renal/urinary system

increased urine protein level ( J:92084 , J:122315 )

albuminuria ( J:122315 )

• mice have excessive urinary albumin compared to wild-type (>10-fold) at 3-4 months

podocyte foot process effacement ( J:127199 )

• foot processes are only focally effaced

dilated renal glomerular capsule ( J:122315 )

• dilated capsules are observed in mice at 3-4 months

abnormal renal glomerulus morphology ( J:7454 , J:127199 )

• 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)

increased mesangial cell number ( J:127199 )

• mild increase in mesangial cells is seen at 20 weeks of age

expanded mesangial matrix ( J:127199 )

• mild increase in mesangial matrix is seen at 20 weeks of age

cortical renal glomerulopathies ( J:122315 )

• glomerulonephritic changes such as hypercellularity, lobularity, dilated capsules and crescent formation or enlarged glomeruli are observed in mice at 3-4 months

glomerulonephritis ( J:7454 , J:92084 , J:122315 , J:127199 )

• 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)

glomerular crescent ( J:122315 )

• crescent formation is observed in mice at 3-4 months

renal glomerulus hypertrophy ( J:122315 )

• enlarged glomeruli are observed in mice at 3-4 months

abnormal kidney physiology ( J:127199 )

• progressive decline in renal function is observed, during progression to end-stage renal disease

behavior/neurological

abnormal spatial learning ( J:14151 )

• 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

impaired coordination ( J:14151 )

• equilibrium is significantly impaired in mice at 18-20 weeks, as measured by performance in rotarod tests

vision/eye

vision/eye phenotype ( J:123192 )

N

conjunctivitis ( J:123192 )

abnormal conjunctival epithelium morphology ( J:123192 )

cardiovascular system

abnormal myocardium layer morphology ( J:14151 )

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

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

vascular inflammation ( J:127199 )

hearing/vestibular/ear

abnormal stria vascularis morphology ( J:3638 )

• 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

abnormal strial intermediate cell morphology ( J:3638 )

• thinned intermediate cell layer

increased or absent threshold for auditory brainstem response ( J:3638 )

• 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

CNS inflammation ( J:14151 )

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

homeostasis/metabolism

increased urine protein level ( J:92084 , J:122315 )

albuminuria ( J:122315 )

• mice have excessive urinary albumin compared to wild-type (>10-fold) at 3-4 months

abnormal enzyme/coenzyme activity ( J:109815 )

• 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

abnormal strial intermediate cell morphology ( J:3638 )

• thinned intermediate cell layer

digestive/alimentary system

salivary gland inflammation ( J:92084 )

endocrine/exocrine glands

salivary gland inflammation ( J:92084 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:123192