Phenotypes Associated with This Genotype

Genotype
MGI:3796615

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: C3.MRL-Fas^lpr/J

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

cardiovascular system

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

mortality/aging

mortality/aging ( J:120650 )

N • when placed under hyperoxic conditions for >5 days, mice do not show increased survival (resistance to hyperoxia) compared to wild-type mice

premature death ( J:7454 )

• 50% mortality is observed at 11.5 months with 90% mortality at 14 months, significantly reduced from wild-type

hematopoietic system

decreased eosinophil cell number ( J:106288 )

• airway eosinophils are decreased with anti-Il5 teatment compared to contol IgG-teated animals at 96 hours

abnormal T cell morphology ( J:7454 )

• (sIg^-, Ly-5(B220⁺) are present at 4 weeks of age in spleen and by 16-20 weeks, represent 80% of cells

abnormal B cell activation ( J:7454 )

• after 10 weeks of age, there is a 2-fold increase in frequency of immunoglobulin-containing and secreting cells in the spleen; this does not occur until abnormal T cells (Ly-5(B220⁺) cells) are found in the spleen

increased immunoglobulin level ( J:7454 )

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

immune system

immune system phenotype ( J:7454 )

N • mice show normal spleen and lymph node cell cytotoxic T cell response to alloantigen

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

decreased eosinophil cell number ( J:106288 )

• airway eosinophils are decreased with anti-Il5 teatment compared to contol IgG-teated animals at 96 hours

abnormal T cell morphology ( J:7454 )

• (sIg^-, Ly-5(B220⁺) are present at 4 weeks of age in spleen and by 16-20 weeks, represent 80% of cells

abnormal B cell activation ( J:7454 )

• after 10 weeks of age, there is a 2-fold increase in frequency of immunoglobulin-containing and secreting cells in the spleen; this does not occur until abnormal T cells (Ly-5(B220⁺) cells) are found in the spleen

increased immunoglobulin level ( J:7454 )

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

enlarged lymph nodes ( J:7454 )

• nodes are 29 times normal size

lymph node hyperplasia ( J:7454 )

• after 10 weeks of age, there is a 3- to 4-fold increase in numbers of B lymphocytes, and after 6 weeks of age, there is a 4- to 5-fold increase in number of null cells (sIg^-, Thy-1^-)

lymph node necrosis ( J:7454 )

• larger lymph nodes often show extensive necrosis

decreased interleukin-2 secretion ( J:7454 )

• after 6 weeks of age, spleen cells show significant decrease in ability to produce Il-2 induced by concanavalin A treatment

increased autoantibody level ( J:7454 )

• marked increase in thymocytotoxic autoantibodies at 6 months is seen

increased anti-nuclear antigen antibody level ( J:7454 )

• mice have significantly increased levels of anti-ssDNA antibodies

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

• antibodies are increased relative to controls

glomerulonephritis ( J:7454 )

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

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:7454 )

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

expanded mesangial matrix ( J:7454 )

• focal increase in mesangial substance

renal glomerular immunoglobulin deposits ( J:7454 )

cellular

increased mesangial cell number ( J:7454 )

• mild mesangial proliferation

increased apoptosis ( J:106288 )

• a trend toward increased apoptosis in airways is observed in anti-Il5 treated mutants after IP-IN OVA challenge

respiratory system

abnormal airway responsiveness ( J:106288 )

• mice intraperitoneally-injected (IP) with ovalbumin (OVA) and subsequently challenged intranasally (IN) with OVA develop airway hyperresponsiveness (AHR) at 48 hours and is significantly sustained at 96 hours but resolves at 6 days, whereas wild-type mice under same paradigm develop AHR at 48 hours but changes in airway resistance resolve by 96 hours

• treatment with anti-Il5 at 48 hours post-IP-IN challenge significantly attenuates AHR