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Former Names B6;D1-Abca1tm1Jdm (Changed: 15-DEC-04 ) Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator John McNeish, Pfizer Central Research Description
Mice that are homozygous for the Abca1-null allele are at greater risk of perinatal lethality. Autopsied pups exhibit perivisceral hemorrhaging. Pups that survive beyond birth have no detectable Abca1 gene transcript in the tissues of the liver. Homozygous females suffer from impaired placental development and are unable to produce litters. Both plasma lipids and lipoproteins are markedly reduced. Plasma cholesterol is decreased by approximately 70%. HDL-C and apoAI are decreased by greater than 99%. LDL-C and apoB are also reduced (70 % and 20%, respectively). Other characteristics observed are an increase in intestinal absorption of dietary cholesterol, an impaired ability for macrophages to engulf apoptotic cells and an accumulation of lipid rich macrophages and type II pneumocytes the lungs. These mice display pathophysiologic hallmarks similar to those associated with Tangier disease and provide a tool suitable for use in studies examining membrane lipid homeostasis.Development
A targeting vector containing a neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 17 and 22 of the Abca1 gene. This portion of the gene encodes the the entire N-terminal ATP-binding cassette. The construct was electroporated into DBA/1LacJ-derived 252 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts to generate chimeric animals.
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 001140 DBA/1LacJ | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Abca1
008596 B6.Cg-Tg(Prnp-Abca1)EHol/J View Strains carrying other alleles of Abca1 (1 strain)
Genetic Quality Control Annual Report
View Related Disease (OMIM) Terms
Related Disease (OMIM) Terms
Tangier Disease; TGD - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Abca1tm1Jdm/Abca1+
DBA/1LacJ
- homeostasis/metabolism phenotype
- abnormal lipid homeostasis (MGI Ref ID J:61679)
- low apolipoprotien A-I level, reduced relative to wild-type on chow and Western-type diets
- low apolipoprotien B level, 20% reduction on chow diet
- abnormal circulating phospholipid level (MGI Ref ID J:61679)
- decreased circulating cholesterol level (MGI Ref ID J:61679)
- respiratory system phenotype
- abnormal lung morphology (MGI Ref ID J:61679)
- microscopic, but not macroscopic, pale foci observed
- foci consisted of type II pneumocytes, lipid-laden macrophages, and cholesterol clefts
Abca1tm1Jdm/Abca1tm1Jdm
DBA/1LacJ
- lethality-prenatal/perinatal
- perinatal lethality (MGI Ref ID J:61679)
- incomplete penetrance
- at weaning, numbers of homozygotes recovered is reduced by about 50% from expected suggesting significant perinatal/postnatal lethality
- lethality-postnatal
- postnatal lethality (MGI Ref ID J:63265)
- numbers of homozygous offspring recovered at weaning is significantly reduced from expected
- cardiovascular system phenotype
- hemorrhage (MGI Ref ID J:63265)
- perivisceral
- digestive/alimentary phenotype
- increased cholesterol absorption (MGI Ref ID J:61679)
- more cholesterol absorbed, relative to wild-type, on both chow and Western diets
- embryogenesis phenotype
- abnormal placenta development (MGI Ref ID J:63265)
- endocrine/exocrine gland phenotype
- enlarged adrenal glands (MGI Ref ID J:60210)
- growth/size phenotype
- decreased body weight (MGI Ref ID J:60210)
- hematopoietic system phenotype
- decreased platelet cell number (MGI Ref ID J:60210)
- enlarged spleen (MGI Ref ID J:60210)
- homeostasis/metabolism phenotype
- abnormal fat-soluble vitamin level (MGI Ref ID J:60210)
- decreased levels of fat-soluble vitamins in plasma
- abnormal lipid homeostasis (MGI Ref ID J:61679)
- low apolipoprotien A-I level, 99.8% reduction relative to wild-type on chow diet and undetectable on Western-type diet
- low apolipoprotien B level, 70% reduction relative to wild-type on chow diet
- abnormal circulating phospholipid level (MGI Ref ID J:61679)
- decreased circulating cholesterol level (MGI Ref ID J:60210)
- ~70% reduction to wild-type on chow diet
- reduced relative to wild-type on Western-type diet
- decreased circulating HDL cholesterol level (MGI Ref ID J:60210)
- 99.5% reduction relative to wild-type on chow diet
- undetectable on Western-type diet
- decreased circulating LDL cholesterol level (MGI Ref ID J:61679)
- 70% reduction relative to wild-type on chow diet
- increased cholesterol absorption (MGI Ref ID J:61679)
- more cholesterol absorbed, relative to wild-type, on both chow and Western diets
- immune system phenotype
- enlarged spleen (MGI Ref ID J:60210)
- impaired macrophage phagocytosis (MGI Ref ID J:63265)
- of apoptotic cells
- reproductive system phenotype
- female infertility (MGI Ref ID J:63265)
- due to abnormal placental development
- respiratory system phenotype
- abnormal lung morphology (MGI Ref ID 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 respiratory alveoli morphology (MGI Ref ID J:61679)
- abnormal architecture; alveolar septae are focally expanded by mild type II penumocyte hypertrophy, macrophages, and aggregates of lymphocytes and plasma cells
- lipid accumulation within alveolar cells
Abca1tm1Jdm/Abca1tm1Jdm
DBA/1-Abca1tm1Jdm/J
- cellular phenotype
- increased cholesterol efflux (MGI Ref ID J:130777)
- homeostasis/metabolism phenotype
- increased cholesterol efflux (MGI Ref ID J:130777)
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Abca1tm1Jdm/Abca1tm1Jdm
Background Not Specified
- homeostasis/metabolism phenotype
- abnormal blood chemistry (MGI Ref ID J:87209)
- strong reduction of plasma beta-sitosterol and campesterol levels
Abca1tm1Jdm/Abca1tm1Jdm
involves: C57BL/6 * DBA/1LacJ
- lethality-prenatal/perinatal
- perinatal lethality (MGI Ref ID J:132254)
- numbers of homozygous offspring recovered at weaning is significantly reduced from expected
- hematopoietic system phenotype
- abnormal thymus morphology (MGI Ref ID 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 phenotype
- abnormal macrophage physiology (MGI Ref ID 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
- abnormal thymus morphology (MGI Ref ID 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
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype (MGI Ref ID J:132254)
- circulating triglyceride levels are normal in fasting mice
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Abca1tm1Jdm related
Cardiovascular Research
Hypocholesterolemia
Metabolism Research
Lipid Metabolism
Mouse/Human Gene Homologs
Tangier's disease
| Allele Symbol | Abca1tm1Jdm | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, John D McNeish | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Abc1-; Abca1-; Abca1-; | ||
| Mutation Made By | John McNeish, Pfizer Central Research | ||
| Strain of Origin | DBA/1LacJ | ||
| Gene Symbol and Name | Abca1, ATP-binding cassette, sub-family A (ABC1), member 1 | ||
| Chromosome | 4 | ||
| Gene Common Name(s) | ABC-1; ABC1; ATP-binding cassette 1; Abc1; CERP; FLJ14958; HDLDT1; MGC164864; MGC165011; TGD; | ||
| General Note | When used in bone marrow transplant into Ldlrtm1Her homozygous mice, Abca1tm1Jdm Abcg1tm1Dgen homozygous cells accelerate the development of atherosclerosis. (J:130777) | ||
| Molecular Note | A 5.7 kb genomic fragment containing exons 17-22 was deleted and replaced with a neomycin selection cassette. These sequences correspond to amino acids 788 to 1093 of the encoded protein. RT-PCR analysis on RNA derived from liver demonstrated that no detectable transcript was produced from this allele in homozygous mice. [MGI Ref ID J:61679] | ||
Genotyping Protocols
Abca1tm1Jdm, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Hamon Y; Broccardo C; Chambenoit O; Luciani MF; Toti F; Chaslin S; Freyssinet JM; Devaux PF; McNeish J; Marguet D; Chimini G. 2000. ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat Cell Biol 2(7):399-406. [PubMed: 10878804] [MGI Ref ID J:63265]
Wahrle SE; Jiang H; Parsadanian M; Legleiter J; Han X; Fryer JD; Kowalewski T; Holtzman DM. 2004. ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE. J Biol Chem 279(39):40987-93. [PubMed: 15269217] [MGI Ref ID J:93336]
Abca1tm1Jdm relatedAdorni MP; Zimetti F; Billheimer JT; Wang N; Rader DJ; Phillips MC; Rothblat GH. 2007. The roles of different pathways in the release of cholesterol from macrophages. J Lipid Res 48(11):2453-62. [PubMed: 17761631] [MGI Ref ID J:127358]
Bates SR; Tao JQ; Collins HL; Francone OL; Rothblat GH. 2005. Pulmonary abnormalities due to ABCA1 deficiency in mice. Am J Physiol Lung Cell Mol Physiol 289(6):L980-9. [PubMed: 16055479] [MGI Ref ID J:105011]
Bravo I; Amigo L; Cohen DE; Nervi F; Rigotti A; Francone O; Zanlungo S. 2007. Role of plasma and liver cholesterol- and lipoprotein-metabolism determinants in LpX formation in the mouse. Biochim Biophys Acta 1770(6):979-88. [PubMed: 17399905] [MGI Ref ID J:121757]
Burns MP; Vardanian L; Pajoohesh-Ganji A; Wang L; Cooper M; Harris DC; Duff K; Rebeck GW. 2006. The effects of ABCA1 on cholesterol efflux and Abeta levels in vitro and in vivo. J Neurochem 98(3):792-800. [PubMed: 16771834] [MGI Ref ID J:119294]
Calpe-Berdiel L; Rotllan N; Palomer X; Ribas V; Blanco-Vaca F; Escola-Gil JC. 2005. Direct evidence in vivo of impaired macrophage-specific reverse cholesterol transport in ATP-binding cassette transporter A1-deficient mice. Biochim Biophys Acta 1738(1-3):6-9. [PubMed: 16413225] [MGI Ref ID J:107452]
Combes V; Coltel N; Alibert M; van Eck M; Raymond C; Juhan-Vague I; Grau GE; Chimini G. 2005. ABCA1 gene deletion protects against cerebral malaria: potential pathogenic role of microparticles in neuropathology. Am J Pathol 166(1):295-302. [PubMed: 15632021] [MGI Ref ID J:95235]
Coutinho JM; Singaraja RR; Kang M; Arenillas DJ; Bertram LN; Bissada N; Staels B; Fruchart JC; Fievet C; Joseph-George AM; Wasserman WW; Hayden MR. 2005. Complete functional rescue of the ABCA1-/- mouse by human BAC transgenesis. J Lipid Res 46(6):1113-23. [PubMed: 15772424] [MGI Ref ID J:99808]
Francone OL; Royer L; Boucher G; Haghpassand M; Freeman A; Brees D; Aiello RJ. 2005. Increased cholesterol deposition, expression of scavenger receptors, and response to chemotactic factors in Abca1-deficient macrophages. Arterioscler Thromb Vasc Biol 25(6):1198-205. [PubMed: 15831807] [MGI Ref ID J:114227]
Francone OL; Subbaiah PV; van Tol A; Royer L; Haghpassand M. 2003. Abnormal phospholipid composition impairs HDL biogenesis and maturation in mice lacking Abca1. Biochemistry 42(28):8569-78. [PubMed: 12859204] [MGI Ref ID J:84572]
Groen AK; Bloks VW; Bandsma RH; Ottenhoff R; Chimini G; Kuipers F. 2001. Hepatobiliary cholesterol transport is not impaired in Abca1-null mice lacking HDL. J Clin Invest 108(6):843-50. [PubMed: 11560953] [MGI Ref ID J:71689]
Hirsch-Reinshagen V; Maia LF; Burgess BL; Blain JF; Naus KE; McIsaac SA; Parkinson PF; Chan JY; Tansley GH; Hayden MR; Poirier J; Van Nostrand W; Wellington CL. 2005. The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease. J Biol Chem 280(52):43243-56. [PubMed: 16207707] [MGI Ref ID J:105900]
Hirsch-Reinshagen V; Zhou S; Burgess BL; Bernier L; McIsaac SA; Chan JY; Tansley GH; Cohn JS; Hayden MR; Wellington CL. 2004. Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain. J Biol Chem 279(39):41197-207. [PubMed: 15269218] [MGI Ref ID J:93331]
Hu W; Abe-Dohmae S; Tsujita M; Iwamoto N; Ogikubo O; Otsuka T; Kumon Y; Yokoyama S. 2008. Biogenesis of HDL by SAA is dependent on ABCA1 in the liver in vivo. J Lipid Res 49(2):386-93. [PubMed: 18033752] [MGI Ref ID J:131875]
Huang ZH; Fitzgerald ML; Mazzone T. 2006. Distinct cellular loci for the ABCA1-dependent and ABCA1-independent lipid efflux mediated by endogenous apolipoprotein E expression. Arterioscler Thromb Vasc Biol 26(1):157-62. [PubMed: 16254198] [MGI Ref ID J:127981]
Iadevaia V; Rinaldi A; Falasca L; Pucillo LP; Alonzi T; Chimini G; Piacentini M. 2006. ATP-binding cassette transporter 1 and transglutaminase 2 act on the same genetic pathway in the apoptotic cell clearance. Cell Death Differ 13(11):1998-2001. [PubMed: 16691213] [MGI Ref ID J:132254]
Iwamoto N; Abe-Dohmae S; Sato R; Yokoyama S. 2006. ABCA7 expression is regulated by cellular cholesterol through the SREBP2 pathway and associated with phagocytosis. J Lipid Res 47(9):1915-27. [PubMed: 16788211] [MGI Ref ID J:114490]
Koldamova R; Staufenbiel M; Lefterov I. 2005. Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice. J Biol Chem 280(52):43224-35. [PubMed: 16207713] [MGI Ref ID J:105902]
Koseki M; Hirano K; Masuda D; Ikegami C; Tanaka M; Ota A; Sandoval JC; Nakagawa-Toyama Y; Sato SB; Kobayashi T; Shimada Y; Ohno-Iwashita Y; Matsuura F; Shimomura I; Yamashita S. 2007. Increased lipid rafts and accelerated lipopolysaccharide-induced tumor necrosis factor-alpha secretion in Abca1-deficient macrophages. J Lipid Res 48(2):299-306. [PubMed: 17079792] [MGI Ref ID J:118227]
Kypreos KE; Zannis VI. 2007. Pathway of biogenesis of apolipoprotein E-containing HDL in vivo with the participation of ABCA1 and LCAT. Biochem J 403(2):359-67. [PubMed: 17206937] [MGI Ref ID J:121679]
McNeish J; Aiello RJ; Guyot D; Turi T; Gabel C; Aldinger C; Hoppe KL; Roach ML; Royer LJ; de Wet J; Broccardo C; Chimini G; Francone OL. 2000. High density lipoprotein deficiency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1. Proc Natl Acad Sci U S A 97(8):4245-50. [PubMed: 10760292] [MGI Ref ID J:61679]
Orso E; Broccardo C; Kaminski WE; Bottcher A; Liebisch G; Drobnik W; Gotz A; Chambenoit O; Diederich W; Langmann T; Spruss T; Luciani MF; Rothe G; Lackner KJ; Chimini G; Schmitz G. 2000. Transport of lipids from golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice. Nat Genet 24(2):192-6. [PubMed: 10655069] [MGI Ref ID J:60210]
Plosch T; Bloks VW; Terasawa Y; Berdy S; Siegler K; Van Der Sluijs F; Kema IP; Groen AK; Shan B; Kuipers F; Schwartz M. 2004. Sitosterolemia in ABC-Transporter G5-deficient mice is aggravated on activation of the liver-X receptor. Gastroenterology 126(1):290-300. [PubMed: 14699507] [MGI Ref ID J:87209]
Plosch T; Kok T; Bloks VW; Smit MJ; Havinga R; Chimini G; Groen AK; Kuipers F. 2002. Increased hepatobiliary and fecal cholesterol excretion upon activation of the liver X receptor is independent of ABCA1. J Biol Chem 277(37):33870-7. [PubMed: 12105210] [MGI Ref ID J:78949]
Selva DM; Hirsch-Reinshagen V; Burgess B; Zhou S; Chan J; McIsaac S; Hayden MR; Hammond GL; Vogl AW; Wellington CL. 2004. The ATP-binding cassette transporter 1 mediates lipid efflux from Sertoli cells and influences male fertility. J Lipid Res 45(6):1040-50. [PubMed: 15026428] [MGI Ref ID J:89906]
Singaraja RR; Stahmer B; Brundert M; Merkel M; Heeren J; Bissada N; Kang M; Timmins JM; Ramakrishnan R; Parks JS; Hayden MR; Rinninger F. 2006. Hepatic ATP-binding cassette transporter A1 is a key molecule in high-density lipoprotein cholesteryl ester metabolism in mice. Arterioscler Thromb Vasc Biol 26(8):1821-7. [PubMed: 16728652] [MGI Ref ID J:127977]
Singaraja RR; Van Eck M; Bissada N; Zimetti F; Collins HL; Hildebrand RB; Hayden A; Brunham LR; Kang MH; Fruchart JC; Van Berkel TJ; Parks JS; Staels B; Rothblat GH; Fievet C; Hayden MR. 2006. Both hepatic and extrahepatic ABCA1 have discrete and essential functions in the maintenance of plasma high-density lipoprotein cholesterol levels in vivo. Circulation 114(12):1301-9. [PubMed: 16940190] [MGI Ref ID J:124718]
Taylor SR; Gonzalez-Begne M; Dewhurst S; Chimini G; Higgins CF; Melvin JE; Elliott JI. 2008. Sequential shrinkage and swelling underlie P2X7-stimulated lymphocyte phosphatidylserine exposure and death. J Immunol 180(1):300-8. [PubMed: 18097031] [MGI Ref ID J:130933]
Wahrle SE; Jiang H; Parsadanian M; Hartman RE; Bales KR; Paul SM; Holtzman DM. 2005. Deletion of Abca1 increases Abeta deposition in the PDAPP transgenic mouse model of Alzheimer disease. J Biol Chem 280(52):43236-42. [PubMed: 16207708] [MGI Ref ID J:105901]
Wahrle SE; Jiang H; Parsadanian M; Kim J; Li A; Knoten A; Jain S; Hirsch-Reinshagen V; Wellington CL; Bales KR; Paul SM; Holtzman DM. 2008. Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J Clin Invest 118(2):671-82. [PubMed: 18202749] [MGI Ref ID J:131400]
Wahrle SE; Jiang H; Parsadanian M; Legleiter J; Han X; Fryer JD; Kowalewski T; Holtzman DM. 2004. ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE. J Biol Chem 279(39):40987-93. [PubMed: 15269217] [MGI Ref ID J:93336]
Wang X; Collins HL; Ranalletta M; Fuki IV; Billheimer JT; Rothblat GH; Tall AR; Rader DJ. 2007. Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J Clin Invest 117(8):2216-24. [PubMed: 17657311] [MGI Ref ID J:123959]
Williamson P; Halleck MS; Malowitz J; Ng S; Fan X; Krahling S; Remaley AT; Schlegel RA. 2007. Transbilayer phospholipid movements in ABCA1-deficient cells. PLoS ONE 2(1):e729. [PubMed: 17710129] [MGI Ref ID J:129392]
Yvan-Charvet L; Ranalletta M; Wang N; Han S; Terasaka N; Li R; Welch C; Tall AR. 2007. Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice. J Clin Invest 117(12):3900-8. [PubMed: 17992262] [MGI Ref ID J:130777]
van der Veen JN; Kruit JK; Havinga R; Baller JF; Chimini G; Lestavel S; Staels B; Groot PH; Groen AK; Kuipers F. 2005. Reduced cholesterol absorption upon PPAR{delta} activation coincides with decreased intestinal expression of NPC1L1. J Lipid Res 46(3):526-34. [PubMed: 15604518] [MGI Ref ID J:96527]
Colony Maintenance
Breeding & Husbandry Chimeric animals were mated with DBA/1J mice for an undetermined number of generations. Upon arrival at The Jackson Laboratory, mice were rederived and while held in a live colony, were maintained as heterozygotes by matings with wildtype DBA/1LacJ. Coat color expected from breeding:Dilute Brown Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 001140 DBA/1LacJ | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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