Phenotypes Associated with This Genotype

Genotype
MGI:5514345

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

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

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