Phenotypes Associated with This Genotype

Genotype
MGI:3037431

• Allelic Composition: Fasl^gld/Fasl^gld
• Genetic Background: C3H/HeJ-Fasl^gld/J

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

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:7306 , J:29572 )

• males survived to mean age of 396 days, females to 369 days, controls survived until 688 days (J:7306)

cardiovascular system

cardiovascular system phenotype ( J:7306 )

N • no defect detected: no vascular disease, including necrotizing arteritis or polyarteritis

hematopoietic system

enlarged spleen ( J:7306 , J:29572 )

• evident after 13 weeks of age (J:7306)

• 4-fold enlargement compared to controls (J:29572)

abnormal T cell differentiation ( J:8267 , J:12002 )

• abnormal cells populating lymph nodes during lymphoproliferation fail to show characteristics of immature or mature T cells: (J:8267)

• express beta-chain of TCR (J:8267)

• exhibit rearrangements of beta-chain genes (J:8267)

• express TCR beta and alpha gene mRNA (J:8267)

• are Thy-1+, Ly-1+, Ly-2-, L3T4-, Ly-5(B220)+, Ly-6+, Ly-22+, Ly-24+, sIg-, ThB-, Ia-, HSA-/+, and PC.1+ (J:8267)

• bind at high levels lectins that normally bind preferentially to B cells (J:8267)

• did not proliferate or generate CTL in response to stimulation with alloantigens (J:8267)

• cells stimulated with Con A failed to produce IL-2 (J:8267)

• abnormal cells populating lymph nodes during lymphoproliferation fail to show characteristics of immature or mature T cells: (J:12002)

• express beta-chain of TCR (J:12002)

• exhibit rearrangements of beta-chain genes (J:12002)

• express TCR beta and alpha gene mRNA (J:12002)

• are Thy-1+, Ly-1+, Ly-2-, L3T4-, Ly-5(B220)+, Ly-6+, Ly-22+, Ly-24+, sIg-, ThB-, Ia-, HSA-/+, and PC.1+ (J:12002)

• bind at high levels lectins that normally bind preferentially to B cells (J:12002)

• did not proliferate or generate CTL in response to stimulation with alloantigens (J:12002)

• cells stimulated with Con A failed to produce IL-2 (J:12002)

anemia ( J:7306 )

• evident in 40% of animals autopsied when moribund

decreased B cell number ( J:29572 )

• 36 to 15%

increased leukocyte cell number ( J:7306 )

increased neutrophil cell number ( J:7306 )

• 2-fold greater than controls

increased lymphocyte cell number ( J:7306 , J:29572 )

• 4-fold greater than controls (J:7306)

• 5-fold increase in peripheral blood lymphocytes (J:29572)

increased T cell number ( J:29572 )

• 59 to 68%

increased immunoglobulin level ( J:7306 , J:29572 )

• development of broad-based hypergammaglobulinemia (J:7306)

• developed broad-based hypergammaglobulinemia (J:29572)

increased IgA level ( J:7306 , J:29572 )

• 10-fold (J:29572)

increased IgG level ( J:29572 )

• 10-fold IgG2a

• 3- to 6-fold IgG1 and IgG2b

increased IgG1 level ( J:7306 )

increased IgG2a level ( J:7306 )

increased IgG2b level ( J:7306 )

increased IgM level ( J:7306 , J:29572 )

decreased cytotoxic T cell cytolysis ( J:17698 )

• in Fas-dependent lysis assays, but not allogeneic targets

homeostasis/metabolism

skin edema ( J:7306 )

• ~25% of those autopsied when moribund showed marked subcutaneous edema

immune system

enlarged spleen ( J:7306 , J:29572 )

• evident after 13 weeks of age (J:7306)

• 4-fold enlargement compared to controls (J:29572)

abnormal T cell differentiation ( J:8267 , J:12002 )

• abnormal cells populating lymph nodes during lymphoproliferation fail to show characteristics of immature or mature T cells: (J:8267)

• express beta-chain of TCR (J:8267)

• exhibit rearrangements of beta-chain genes (J:8267)

• express TCR beta and alpha gene mRNA (J:8267)

• are Thy-1+, Ly-1+, Ly-2-, L3T4-, Ly-5(B220)+, Ly-6+, Ly-22+, Ly-24+, sIg-, ThB-, Ia-, HSA-/+, and PC.1+ (J:8267)

• bind at high levels lectins that normally bind preferentially to B cells (J:8267)

• did not proliferate or generate CTL in response to stimulation with alloantigens (J:8267)

• cells stimulated with Con A failed to produce IL-2 (J:8267)

• abnormal cells populating lymph nodes during lymphoproliferation fail to show characteristics of immature or mature T cells: (J:12002)

• express beta-chain of TCR (J:12002)

• exhibit rearrangements of beta-chain genes (J:12002)

• express TCR beta and alpha gene mRNA (J:12002)

• are Thy-1+, Ly-1+, Ly-2-, L3T4-, Ly-5(B220)+, Ly-6+, Ly-22+, Ly-24+, sIg-, ThB-, Ia-, HSA-/+, and PC.1+ (J:12002)

• bind at high levels lectins that normally bind preferentially to B cells (J:12002)

• did not proliferate or generate CTL in response to stimulation with alloantigens (J:12002)

• cells stimulated with Con A failed to produce IL-2 (J:12002)

decreased B cell number ( J:29572 )

• 36 to 15%

increased leukocyte cell number ( J:7306 )

increased neutrophil cell number ( J:7306 )

• 2-fold greater than controls

increased lymphocyte cell number ( J:7306 , J:29572 )

• 4-fold greater than controls (J:7306)

• 5-fold increase in peripheral blood lymphocytes (J:29572)

increased T cell number ( J:29572 )

• 59 to 68%

increased immunoglobulin level ( J:7306 , J:29572 )

• development of broad-based hypergammaglobulinemia (J:7306)

• developed broad-based hypergammaglobulinemia (J:29572)

increased IgA level ( J:7306 , J:29572 )

• 10-fold (J:29572)

increased IgG level ( J:29572 )

• 10-fold IgG2a

• 3- to 6-fold IgG1 and IgG2b

increased IgG1 level ( J:7306 )

increased IgG2a level ( J:7306 )

increased IgG2b level ( J:7306 )

increased IgM level ( J:7306 , J:29572 )

decreased cytotoxic T cell cytolysis ( J:17698 )

• in Fas-dependent lysis assays, but not allogeneic targets

abnormal lymph node morphology ( J:7306 )

enlarged lymph nodes ( J:7306 , J:29572 )

• enlarged peripheral lymph nodes evident at 13 weeks of age, abdominal evident shortly thereafter (J:7306)

• evidence of chronic inflammation at autopsy, with proliferation of lymphocytes and admixtures of histiocytes and plasma cells observed, fibrosis and multinucleated giant cells also frequently observed (J:7306)

• 50-fold heavier at 20 weeks of age than controls (J:29572)

increased autoantibody level ( J:7306 )

• thymocyte-binding autoantibody present

increased anti-nuclear antigen antibody level ( J:7306 , J:29572 )

• high titers of antinuclear autoantibodies evident by 16 weeks of age in all mice assayed (J:7306)

• high titers of antinuclear autoantibodies evident at 14 weeks of age (J:29572)

increased anti-double stranded DNA antibody level ( J:7306 )

• high concentrations of anti-dsDNA autoantibodies present

interstitial pneumonia ( J:7306 )

• lung inflammation resembling interstitial pneumonitis evident in virtually all animals autopsied when moribund

renal/urinary system

renal/urinary system phenotype ( J:7306 )

N • despite glomerular deposition of immune complexes, no, or very little, glomerulonephritis was observed

respiratory system

interstitial pneumonia ( J:7306 )

• lung inflammation resembling interstitial pneumonitis evident in virtually all animals autopsied when moribund

neoplasm

neoplasm ( J:108303 )

N • regression of transplanted SCCVII tumors by gene therapy treatment with Il12b is normal

integument

skin edema ( J:7306 )

• ~25% of those autopsied when moribund showed marked subcutaneous edema

growth/size/body

enlarged spleen ( J:7306 , J:29572 )

• evident after 13 weeks of age (J:7306)

• 4-fold enlargement compared to controls (J:29572)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autoimmune lymphoproliferative syndrome		DOID:6688	OMIM:601859	J:7306 , J:29572