Mouse Genome Informatics
hm1
     Abca1tm1Jdm/Abca1tm1Jdm
DBA/1-Abca1tm1Jdm/J
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
cellular

homeostasis/metabolism


Mouse Genome Informatics
hm2
     Abca1tm1Jdm/Abca1tm1Jdm
DBA/1LacJ-Abca1tm1Jdm
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype

Pulmonary lesions in Abca1tm1Jdm/Abca1tm1Jdm mice

mortality/aging
partial perinatal lethality ( J:61679 )
• incomplete penetrance
• at weaning, numbers of homozygotes recovered is reduced by about 50% from expected suggesting significant perinatal/postnatal lethality
partial postnatal lethality ( J:63265 )
• numbers of homozygous offspring recovered at weaning is significantly reduced from expected

cardiovascular system
hemorrhage ( J:63265 )
• perivisceral

digestive/alimentary system
increased intestinal cholesterol absorption ( J:61679 )
• more cholesterol absorbed, relative to wild-type, on both chow and Western diets

embryogenesis

endocrine/exocrine glands

growth/size

hematopoietic system

homeostasis/metabolism
abnormal lipid homeostasis ( J:61679 )
• low apolipoprotein A-I level, 99.8% reduction relative to wild-type on chow diet and undetectable on Western-type diet
• low apolipoprotein B level, 70% reduction relative to wild-type on chow diet
increased intestinal cholesterol absorption ( J:61679 )
• more cholesterol absorbed, relative to wild-type, on both chow and Western diets
decreased circulating cholesterol level ( J:60210 , J:61679 )
• ~70% reduction to wild-type on chow diet (J:61679)
• reduced relative to wild-type on Western-type diet (J:61679)
decreased circulating HDL cholesterol level ( J:60210 , J:61679 )
• 99.5% reduction relative to wild-type on chow diet (J:61679)
• undetectable on Western-type diet (J:61679)
decreased circulating LDL cholesterol level ( J:61679 )
• 70% reduction relative to wild-type on chow diet
abnormal fat-soluble vitamin level ( J:60210 )
• decreased levels of fat-soluble vitamins in plasma

immune system
impaired macrophage phagocytosis ( J:63265 )
• of apoptotic cells

reproductive system
female infertility ( J:63265 )
• due to abnormal placental development (J:63265)

respiratory system
abnormal lung morphology ( J:61679 )
• macroscopic and microscopic pale foci in 5-10% of parenchyma in mice 7 months or older, increasingly prevalent with age
• foci consisted of type II pneumocytes, lipid-laden macrophages, and cholesterol clefts
abnormal pulmonary alveolus morphology ( J:61679 )
• abnormal architecture; alveolar septae are focally expanded by mild type II pneumocyte hypertrophy, macrophages, and aggregates of lymphocytes and plasma cells
• lipid accumulation within alveolar cells

Mouse Models of Human Disease
 OMIM IDRef(s)
Tangier Disease; TGD 205400 J:61679


Mouse Genome Informatics
hm3
     Abca1tm1Jdm/Abca1tm1Jdm
involves: C57BL/6 * DBA/1LacJ
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
partial perinatal lethality ( J:132254 )
• numbers of homozygous offspring recovered at weaning is significantly reduced from expected

hematopoietic system
abnormal thymus morphology ( J:132254 )
• massive thymic involution induced by dexamethasone treatment results in significant decrease in thymic weight and cellularity compared to wild-type, and similar to single null mice

immune system
abnormal thymus morphology ( J:132254 )
• massive thymic involution induced by dexamethasone treatment results in significant decrease in thymic weight and cellularity compared to wild-type, and similar to single null mice
impaired macrophage phagocytosis ( J:132254 )
• isolated peritoneal macrophages exposed to apoptotic thymocytes internalize similar numbers of cells (1-2 cells) as wild-type after 15-30 minutes, but this number does not increase with time as with wild-type which internalize 4-5 cells at 60-120 minutes
• after massive thymic involution induced by dexamethasone treatment, macrophages display reduced phagocytosis ability compared to wild-type, and similar to single-null mice

homeostasis/metabolism
homeostasis/metabolism phenotype ( J:132254 )
N
• circulating triglyceride levels are normal in fasting mice (J:132254)
decreased circulating cholesterol level ( J:132254 )
• levels are reduced compared to adult wild-type or Tgm2-null mice
decreased circulating HDL cholesterol level ( J:132254 )
• adult mice show nearly complete loss of HDL cholesterol in fasting mice


Mouse Genome Informatics
hm4
     Abca1tm1Jdm/Abca1tm1Jdm
involves: DBA/1LacJ
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
homeostasis/metabolism
abnormal circulating plant sterol concentration ( J:87209 )
• strong reduction of plasma beta-sitosterol and campesterol levels


Mouse Genome Informatics
ht5
     Abca1tm1Jdm/Abca1+
DBA/1LacJ-Abca1tm1Jdm
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
homeostasis/metabolism
abnormal lipid homeostasis ( J:61679 )
• low apolipoprotein A-I level, reduced relative to wild-type on chow and Western-type diets
• low apolipoprotein B level, 20% reduction on chow diet
decreased circulating HDL cholesterol level ( J:61679 )
• reduced relative to wild-type on chow and Western-type diets
decreased circulating LDL cholesterol level ( J:61679 )
• 20% reduction on chow diet

respiratory system
abnormal lung morphology ( J:61679 )
• microscopic, but not macroscopic, pale foci observed
• foci consisted of type II pneumocytes, lipid-laden macrophages, and cholesterol clefts


Mouse Genome Informatics
cx6
     Abca1tm1Jdm/Abca1tm1Jdm
Abcg1tm1Dgen/Abcg1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6 * DBA * DBA/1LacJ
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
hematopoietic system
decreased monocyte cell number ( J:190966 )
• from in vitro bone marrow cultures treated with G-CSF
increased neutrophil cell number ( J:190966 )
• from in vitro bone marrow cultures treated with G-CSF or IL3
increased monocyte cell number ( J:190966 )
• from in vitro bone marrow cultures treated with IL3
abnormal bone marrow cell morphology/development ( J:190966 )
• mice exhibit a decrease in heterogeneous distribution of bone tissue material properties compared with wild-type mice
abnormal hematopoietic system physiology ( J:190966 )
• hematopoietic stem and multipotential progenitor cell (HSPC) mobilization is enhanced that is bone marrow- and G-CSF-dependent driven by increased IL23/IL17

skeleton

immune system
decreased monocyte cell number ( J:190966 )
• from in vitro bone marrow cultures treated with G-CSF
increased neutrophil cell number ( J:190966 )
• from in vitro bone marrow cultures treated with G-CSF or IL3
increased monocyte cell number ( J:190966 )
• from in vitro bone marrow cultures treated with IL3


Mouse Genome Informatics
cx7
     Abca1tm1Jdm/Abca1tm1Jdm
Abcg1tm1Dgen/Abcg1tm1Dgen
Tg(APOA1)1Rub/0
involves: 129P2/OlaHsd * C57BL/6 * DBA * DBA/1LacJ
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
hematopoietic system
abnormal hematopoietic system physiology ( J:190966 )
• in bone marrow transplants experiments, hematopoietic stem and multipotential progenitor cell (HSPC) exhibit reduced mobilization compared with Abca1tm1Jdm Abcg1tm1Dgen double homozygotes


Mouse Genome Informatics
cx8
     Abca1tm1Jdm/Abca1tm1Jdm
Abcg1tm1Dgen/Abcg1tm1Dgen
Apoetm1Unc/Apoetm1Unc
involves: 129P2/OlaHsd * C57BL/6 * DBA * DBA/1LacJ
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
hematopoietic system
abnormal hematopoietic system physiology ( J:190966 )
• mice fed a high fat diet exhibit increased hematopoietic stem and multipotential progenitor cell (HSPC) mobilization compared with wild-type mice
• however, treatment with recombinant HDL suppresses this increase


Mouse Genome Informatics
cx9
     Abca1tm1Jdm/Abca1tm1Jdm
Abcg1tm1Dgen/Abcg1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6 * DBA/1LacJ
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
immune system
abnormal cytokine secretion ( J:130777 )
• mice exhibit increased secretion of TNF-alpha, IL-6, IL-1beta, and IL-12 compared to wild-type mice
abnormal chemokine secretion ( J:130777 )
• mice exhibit increased secretion of MIP-1alpha, MIP-2, growth-regulated oncogene alpha and MCP-1 compared to wild-type mice

cellular

homeostasis/metabolism


Mouse Genome Informatics
cx10
     Abca1tm1Jdm/Abca1tm1Jdm
Tgm2tm1Gml/Tgm2tm1Gml
involves: C57BL/6 * DBA/1LacJ
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging

hematopoietic system
abnormal thymus morphology ( J:132254 )
• massive thymic involution induced by dexamethasone treatment results in significant decrease in thymic weight and cellularity compared to wild-type, and similar to single null mice

immune system
abnormal thymus morphology ( J:132254 )
• massive thymic involution induced by dexamethasone treatment results in significant decrease in thymic weight and cellularity compared to wild-type, and similar to single null mice
impaired macrophage phagocytosis ( J:132254 )
• isolated peritoneal macrophages exposed to apoptotic thymocytes internalize similar numbers of cells (1-2 cells) as wild-type after 15-30 minutes, but this number does not increase with time as with wild-type which internalize 4-5 cells at 60-120 minutes
• after massive thymic involution induced by dexamethasone treatment, macrophages display reduced phagocytosis ability compared to wild-type, and similar to single-null mice

homeostasis/metabolism
homeostasis/metabolism phenotype ( J:132254 )
N
• circulating triglyceride levels are normal in fasting mice (J:132254)
decreased circulating cholesterol level ( J:132254 )
• levels are reduced compared to adult wild-type or Tgm2-null mice
decreased circulating HDL cholesterol level ( J:132254 )
• adult mice show nearly complete loss of HDL cholesterol in fasting mice


Mouse Genome Informatics
cx11
     Abca1tm1Jdm/Abca1tm1Jdm
Tg(Thy1-APP)3Somm/0
involves: C57BL/6J * DBA/1LacJ * DBA/2
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
partial preweaning lethality ( J:105902 )
• fewer than expected mice are present at weaning

nervous system
intracerebral hemorrhage ( J:105902 )
• mice exhibit more cerebral amyloid angiopathy-associated cerebral hemorrhage than Tg(Thy1-APP)3Somm mice
cerebral amyloid angiopathy ( J:105902 )
• at 13 months, mice exhibit more cerebral amyloid angiopathy than in Tg(Thy1-APP)3Somm mice

other phenotype
amyloidosis ( J:105902 )
• mice exhibit a 2-fold increase in insoluble beta-amyloid in the brain compared with Tg(Thy1-APP)3Somm mice
cerebral amyloid angiopathy ( J:105902 )
• at 13 months, mice exhibit more cerebral amyloid angiopathy than in Tg(Thy1-APP)3Somm mice

cardiovascular system
intracerebral hemorrhage ( J:105902 )
• mice exhibit more cerebral amyloid angiopathy-associated cerebral hemorrhage than Tg(Thy1-APP)3Somm mice