Phenotypes associated with this allele

• Allele Symbol: Fasl^gld
• Allele Name: generalized lymphoproliferative disease
• Allele ID: MGI:1856384
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fasl^gld/Fasl^gld	B6.C3-Fasl^gld	MGI:5514349
hm2	Fasl^gld/Fasl^gld	B6Smn.C3-Fasl^gld/J	MGI:3707400
hm3	Fasl^gld/Fasl^gld	C3H/HeJ-Fasl^gld	MGI:3799212
hm4	Fasl^gld/Fasl^gld	C3H/HeJ-Fasl^gld/J	MGI:3037431
hm5	Fasl^gld/Fasl^gld	involves: C3H/HeJ	MGI:4430566
hm6	Fasl^gld/Fasl^gld	involves: C3H/HeJ * C57BL/6	MGI:4365591
hm7	Fasl^gld/Fasl^gld	involves: C3H/HeJ * CBA	MGI:3800573
cx8	Apoe^tm1Unc/Apoe^tm1Unc Fasl^gld/Fasl^gld	B6.Cg-Fasl^gld Apoe^tm1Unc	MGI:5514345
cx9	Fasl^gld/Fasl^gld Ighm^tm1Cgn/Ighm^tm1Cgn	involves: 129S2/SvPas * C3H/HeJ * C57BL/6	MGI:3767450

Genotype
MGI:5514349

hm1

• Allelic Composition: Fasl^gld/Fasl^gld
• Genetic Background: B6.C3-Fasl^gld

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

immune system

impaired macrophage phagocytosis ( J:91058 )

• clearance of apoptotic material by macrophages is reduced

• mutants infused with lysophosphatidylcholine (LPC) show a greater accumulation of apoptotic debris in lymph nodes than similarly treated wild-type mice

enlarged spleen ( J:91058 )

increased spleen weight ( J:91058 )

abnormal lymph node morphology ( J:91058 )

• mutants exhibit an increase in apoptotic material in the lymph nodes

enlarged lymph nodes ( J:91058 )

• increase in lymph node size and weight

increased autoantibody level ( J:91058 )

• serum levels of anticardiolipin antibody are modestly elevated on a normal diet and are further elevated on a Western diet

increased anti-nuclear antigen antibody level ( J:91058 )

• high titers of anti-nuclear antigen antibodies (ANAs) on normal and Western diet

cellular

increased apoptosis ( J:91058 )

• mutants exhibit an increase in apoptotic material in the lymph nodes

impaired macrophage phagocytosis ( J:91058 )

• clearance of apoptotic material by macrophages is reduced

• mutants infused with lysophosphatidylcholine (LPC) show a greater accumulation of apoptotic debris in lymph nodes than similarly treated wild-type mice

hematopoietic system

impaired macrophage phagocytosis ( J:91058 )

• clearance of apoptotic material by macrophages is reduced

• mutants infused with lysophosphatidylcholine (LPC) show a greater accumulation of apoptotic debris in lymph nodes than similarly treated wild-type mice

enlarged spleen ( J:91058 )

increased spleen weight ( J:91058 )

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:91058 )

N • lipid levels are normal

cardiovascular system

cardiovascular system phenotype ( J:91058 )

N • mutants do not develop atherosclerotic lesions and do not show macrophage or T cell infiltration in the aorta

growth/size/body

enlarged spleen ( J:91058 )

increased spleen weight ( J:91058 )

Genotype
MGI:3707400

hm2

• Allelic Composition: Fasl^gld/Fasl^gld
• Genetic Background: B6Smn.C3-Fasl^gld/J

immune system

decreased granulocyte number ( J:136745 )

• mice infected with 500 CFU of S. aureus show half the number of granulocytes infiltrate the eyes compared to infected wild-type eyes at 24 hours after infection

abnormal NK cell physiology ( J:115033 )

• continuous treatment with recombinant murine IL12 results in sustained recruitment of NK cells to the liver

abnormal osteoclast physiology ( J:127179 )

• osteoclasts are resistant to estrogen induced apoptosis

CNS inflammation ( J:120427 )

• by 7 days after TMEV infection, inflammation is present in the meninges and gray matter, but decreases by 21 days, although not as much as in controls (B6)

brain inflammation ( J:120427 )

• by 7 days after TMEV infection, inflammation is present, decreasing slightly by 21 days, but widespread tissue damage is present, similar to controls (B6)

• tissue damage is less frequent at 45 days than in Prf-null mice

• at 180 days, some degree of brain pathology is still present, while inflammation is absent in controls

eye inflammation ( J:136745 )

• mice infected with 500 CFU of S. aureus show signs of severe intraocular inflammation and tissue destruction

• mice infected with 500 CFU of S. aureus show half the number of granulocytes infiltrate the eyes compared to infected wild-type eyes at 24 hours after infection

liver inflammation ( J:135830 )

• after BDL, necroinflammatory foci and lymphocytic infiltration are obviously less than in controls

increased susceptibility to bacterial infection ( J:136745 )

• mice infected with 500 CFU of S. aureus have drastically elevated number of S. aureus CFU compared to similarly-infected wild-type mice

increased susceptibility to Picornaviridae infection ( J:120427 )

• inflammation and tissue damage in the brain are slightly greater than in control, resistant mice at 45 and 180 days

reproductive system

abnormal male germ cell apoptosis ( J:146994 )

♂ • sperm apoptosis is decreased compared to in wild-type mice

increased sperm number ( J:146994 )

♂ • epididymal sperm count is increased compared to in wild-type mice due to decreased sperm apoptosis

liver/biliary system

decreased hepatocyte apoptosis ( J:135830 )

• hepatocyte cell death is reduced compared to controls after BDL

liver inflammation ( J:135830 )

• after BDL, necroinflammatory foci and lymphocytic infiltration are obviously less than in controls

abnormal hepatocyte morphology ( J:135830 )

• confluent foci of feathery hepatocyte degeneration due to bile acid cytotoxicity are significantly reduced compared to controls 24 hours after BDL

focal hepatic necrosis ( J:135830 )

• necroinflammatory foci after BDL are reduced in number compared to controls after BDL

vision/eye

eye inflammation ( J:136745 )

• mice infected with 500 CFU of S. aureus show signs of severe intraocular inflammation and tissue destruction

• mice infected with 500 CFU of S. aureus show half the number of granulocytes infiltrate the eyes compared to infected wild-type eyes at 24 hours after infection

abnormal eye electrophysiology ( J:136745 )

• mice have only 7% of b-wave amplitude remaining at 24 hours after infection with 500CFU S. aureus, and show no detectable retinal function after this time point

nervous system

CNS inflammation ( J:120427 )

• by 7 days after TMEV infection, inflammation is present in the meninges and gray matter, but decreases by 21 days, although not as much as in controls (B6)

brain inflammation ( J:120427 )

• by 7 days after TMEV infection, inflammation is present, decreasing slightly by 21 days, but widespread tissue damage is present, similar to controls (B6)

• tissue damage is less frequent at 45 days than in Prf-null mice

• at 180 days, some degree of brain pathology is still present, while inflammation is absent in controls

demyelination ( J:120427 )

• at 45 days and later time points, there is minimal or no pathology, similar to controls and in contrast to Prf-null mice

homeostasis/metabolism

decreased circulating alanine transaminase level ( J:135830 )

• one day following bile duct ligation (BDL), serum ALT levels are significantly lower than controls

hematopoietic system

decreased granulocyte number ( J:136745 )

• mice infected with 500 CFU of S. aureus show half the number of granulocytes infiltrate the eyes compared to infected wild-type eyes at 24 hours after infection

abnormal NK cell physiology ( J:115033 )

• continuous treatment with recombinant murine IL12 results in sustained recruitment of NK cells to the liver

abnormal osteoclast physiology ( J:127179 )

• osteoclasts are resistant to estrogen induced apoptosis

skeleton

abnormal osteoclast physiology ( J:127179 )

• osteoclasts are resistant to estrogen induced apoptosis

cellular

abnormal male germ cell apoptosis ( J:146994 )

♂ • sperm apoptosis is decreased compared to in wild-type mice

decreased hepatocyte apoptosis ( J:135830 )

• hepatocyte cell death is reduced compared to controls after BDL

Genotype
MGI:3799212

hm3

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

hematopoietic system

abnormal T cell morphology ( J:8267 )

• lymph node cells (T cell origin) are abnormal; cells are Ly-2^-/L3T4^-/surface Ig^-

abnormal T cell physiology ( J:8267 )

• cells do not generate CTL in response to stimulation with alloantigens

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

homeostasis/metabolism

abnormal interleukin level ( J:8267 )

• stimulation with concanavalin A does not induce cells to produce Il2

immune system

abnormal T cell morphology ( J:8267 )

• lymph node cells (T cell origin) are abnormal; cells are Ly-2^-/L3T4^-/surface Ig^-

abnormal T cell physiology ( J:8267 )

• cells do not generate CTL in response to stimulation with alloantigens

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

abnormal interleukin level ( J:8267 )

• stimulation with concanavalin A does not induce cells to produce Il2

nervous system

decreased neuron apoptosis ( J:124252 )

• very low levels of apoptosis (15%) compared to wild-type (60%) are seen when cortical neurons are treated with Abeta25-35 or Abeta1-40 peptides

• neuron viability is comparable to wild-type when grown in absence of Abeta or if treated with KCN which induces necrotic cell death

cellular

decreased neuron apoptosis ( J:124252 )

• very low levels of apoptosis (15%) compared to wild-type (60%) are seen when cortical neurons are treated with Abeta25-35 or Abeta1-40 peptides

• neuron viability is comparable to wild-type when grown in absence of Abeta or if treated with KCN which induces necrotic cell death

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

Genotype
MGI:3037431

hm4

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

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

Genotype
MGI:4430566

hm5

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

immune system

enlarged spleen ( J:171440 )

increased spleen weight ( J:171440 )

abnormal osteoclast physiology ( J:156947 )

• 17beta-estradiol, dihydrotestosterone, and pyrazole all fail to stimulate osteoclast apoptosis in culture

enlarged lymph nodes ( J:171440 )

skeleton

abnormal osteoclast physiology ( J:156947 )

• 17beta-estradiol, dihydrotestosterone, and pyrazole all fail to stimulate osteoclast apoptosis in culture

hematopoietic system

enlarged spleen ( J:171440 )

increased spleen weight ( J:171440 )

abnormal osteoclast physiology ( J:156947 )

• 17beta-estradiol, dihydrotestosterone, and pyrazole all fail to stimulate osteoclast apoptosis in culture

growth/size/body

enlarged spleen ( J:171440 )

increased spleen weight ( J:171440 )

Genotype
MGI:4365591

hm6

• Allelic Composition: Fasl^gld/Fasl^gld
• Genetic Background: involves: C3H/HeJ * C57BL/6

mortality/aging

premature death ( J:153501 )

immune system

immune system phenotype ( J:153501 )

N • mice mount a normal immune response to influenza

enlarged spleen ( J:153501 )

• by 14 weeks

increased T cell number ( J:153501 )

• TCRalpha/beta+CD4-CD8-B220+ T cells

increased IgE level ( J:153501 )

increased IgG level ( J:153501 )

increased IgG1 level ( J:153501 )

increased IgG2a level ( J:153501 )

increased IgG2b level ( J:153501 )

increased circulating tumor necrosis factor level ( J:153501 )

enlarged lymph nodes ( J:153501 )

• by 14 weeks

increased susceptibility to systemic lupus erythematosus ( J:153501 )

• by 57 weeks, 15% of mice develop fatal SLE-like autoimmune kidney disease unlike wild-type mice

increased anti-nuclear antigen antibody level ( J:153501 )

• in some mice

dermatitis ( J:153501 )

• in 10% of mice and later than in Fasl^tm1.1Ast homozygotes

neoplasm

increased histiocytic sarcoma incidence ( J:153501 )

• rare

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:153501 )

decreased susceptibility to injury ( J:76811 )

• following pancreatic duct ligation, mice exhibit virtually no acinar cell loss or ductal metaplasia compared with similarly treated wild-type mice

• following pancreatic duct ligation, mice exhibit less acinar cell apoptosis than similarly treated wild-type mice

• however, areas of inflammation and fibrosis are sometimes observed following pancreatic duct ligation

hematopoietic system

enlarged spleen ( J:153501 )

• by 14 weeks

increased T cell number ( J:153501 )

• TCRalpha/beta+CD4-CD8-B220+ T cells

increased IgE level ( J:153501 )

increased IgG level ( J:153501 )

increased IgG1 level ( J:153501 )

increased IgG2a level ( J:153501 )

increased IgG2b level ( J:153501 )

integument

dermatitis ( J:153501 )

• in 10% of mice and later than in Fasl^tm1.1Ast homozygotes

growth/size/body

enlarged spleen ( J:153501 )

• by 14 weeks

Genotype
MGI:3800573

hm7

• Allelic Composition: Fasl^gld/Fasl^gld
• Genetic Background: involves: C3H/HeJ * CBA

reproductive system

reproductive system phenotype ( J:114219 )

N • at 2 days after estrogen deprivation induced by gonadectomy, mutant females show a normal estrous cycle and a similar degree of vaginal regression (as measured by the decrease in vaginal organ weight) relative to wild-type females, indicating normal Fas-mediated vaginal cell death

Genotype
MGI:5514345

cx8

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Fasl^gld/Fasl^gld
• Genetic Background: B6.Cg-Fasl^gld Apoe^tm1Unc

cardiovascular system

atherosclerotic lesions ( J:91058 , J:200141 )

• mutants on a Western diet for 12 weeks exhibit atherosclerotic lesions in the aorta (J:91058)

• aortae show higher levels of macrophage and T cell extravasation within lesions and higher levels of apoptotic cells within lesions than in single Apoe homozygotes (J:91058)

• treatment with mycophenolate mofetil decreases the severity of atherosclerosis seen in mice fed a Western diet (J:200141)

increased susceptibility to atherosclerosis ( J:91058 )

• lesion area of mutants fed a Western diet is greater than in single Apoe homozygotes, with a 3-fold increase in plaque area

• mutants on a normal diet exhibit larger atherosclerotic lesion area than single Apoe homozygotes

blood vessel inflammation ( J:91058 )

• aortae show macrophage and T cell extravasation within atherosclerotic lesions, showing a greater increase in macrophages and T cells than in single Apoe homozygotes

cellular

increased apoptosis ( J:91058 )

• mutants exhibit a 40% higher frequency of apoptotic material in the lymph nodes than single Fasl homozygotes

• higher levels of apoptotic cells are seen within atherosclerotic lesions than in single Apoe homozygotes

impaired macrophage phagocytosis ( J:91058 )

• clearance of apoptotic material by macrophages is reduced even further compared to single Fasl homozygotes when fed a Western diet

hematopoietic system

impaired macrophage phagocytosis ( J:91058 )

• clearance of apoptotic material by macrophages is reduced even further compared to single Fasl homozygotes when fed a Western diet

enlarged spleen ( J:91058 )

• on a Western and normal diet

increased spleen weight ( J:91058 , J:200141 )

• spleen weight is increased to almost double that seen in single Fasl homozygotes on a Western diet and 5-fold that seen in wild-type or single Apoe homozygotes (J:91058)

• treatment with mycophenolate mofetil, an immunosuppressive agent, reduces spleen weight (J:200141)

increased T cell number ( J:91058 )

• total number of all T cell subsets is increased in the lymph nodes, however no differences in the percentages of CD4+, CD8+ or double negative T cells are seen

increased IgG level ( J:91058 )

• IgG levels are elevated on both the normal and Western diet

homeostasis/metabolism

decreased circulating HDL cholesterol level ( J:91058 )

• decrease in high density lipoprotein levels compared to wild-type mice

increased circulating cholesterol level ( J:91058 , J:200141 )

• mutants become hypercholesterolemic on a Western diet but to a lesser extent than single Apoe homozygotes (J:91058)

increased circulating LDL cholesterol level ( J:91058 )

• increase in low density lipoprotein (LDL) levels compared to wild-type mice

increased circulating VLDL cholesterol level ( J:91058 )

• increase in very low density lipoprotein (VLDL) levels compared to wild-type mice, however levels are lower than in single Apoe homozygotes

increased circulating triglyceride level ( J:91058 )

• mild increase in plasma triglyceride levels when fed a Western or normal diet

increased urine protein level ( J:91058 )

immune system

blood vessel inflammation ( J:91058 )

• aortae show macrophage and T cell extravasation within atherosclerotic lesions, showing a greater increase in macrophages and T cells than in single Apoe homozygotes

impaired macrophage phagocytosis ( J:91058 )

• clearance of apoptotic material by macrophages is reduced even further compared to single Fasl homozygotes when fed a Western diet

enlarged spleen ( J:91058 )

• on a Western and normal diet

increased spleen weight ( J:91058 , J:200141 )

• spleen weight is increased to almost double that seen in single Fasl homozygotes on a Western diet and 5-fold that seen in wild-type or single Apoe homozygotes (J:91058)

• treatment with mycophenolate mofetil, an immunosuppressive agent, reduces spleen weight (J:200141)

increased T cell number ( J:91058 )

• total number of all T cell subsets is increased in the lymph nodes, however no differences in the percentages of CD4+, CD8+ or double negative T cells are seen

increased IgG level ( J:91058 )

• IgG levels are elevated on both the normal and Western diet

abnormal lymph node morphology ( J:91058 )

• mutants exhibit a 40% higher frequency of apoptotic material in the lymph nodes than single Fasl homozygotes

enlarged lymph nodes ( J:91058 , J:200141 )

• increase in lymph node size and weight both on the Western and normal diets; this increase is larger than in single Fasl homozygotes (J:91058)

increased autoantibody level ( J:91058 )

• serum levels of anti-cardiolipin antibody are about 4-fold higher than in single Fasl homozygotes on both the normal and Western diets

increased anti-nuclear antigen antibody level ( J:91058 , J:200141 )

• anti-nuclear antibody (ANA) titers are elevated compared to single Fasl homozygotes on a normal diet and further elevated by Western diet (J:91058)

• treatment with mycophenolate mofetil decreases the anti-nuclear antibody titer (J:200141)

kidney inflammation ( J:200141 )

• infiltration of inflammatory cells and modest crest formation

renal/urinary system

increased urine protein level ( J:91058 )

kidney inflammation ( J:200141 )

• infiltration of inflammatory cells and modest crest formation

abnormal renal glomerulus morphology ( J:91058 , J:200141 )

• kidneys have larger, more cellular glomeruli (J:91058)

• treatment with mycophenolate mofetil decreases glomerular tuft size and cell count (J:200141)

growth/size/body

enlarged spleen ( J:91058 )

• on a Western and normal diet

increased spleen weight ( J:91058 , J:200141 )

• spleen weight is increased to almost double that seen in single Fasl homozygotes on a Western diet and 5-fold that seen in wild-type or single Apoe homozygotes (J:91058)

• treatment with mycophenolate mofetil, an immunosuppressive agent, reduces spleen weight (J:200141)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:91058 , J:200141

Genotype
MGI:3767450

cx9

• Allelic Composition: Fasl^gld/Fasl^gld; Ighm^tm1Cgn/Ighm^tm1Cgn
• Genetic Background: involves: 129S2/SvPas * C3H/HeJ * C57BL/6

immune system

immune system phenotype ( J:119584 )

N • mice have high levels of IgG after birth that rise to levels similar to wild-type littermates by 90 days after birth