Description

Strain Information

Type Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   01-MAR-06 Breeding Considerations This strain is a good breeder. Species laboratory mouse Generation F?+N1F11 (17-SEP-12) Generation Definitions   Donating Investigator Dr. Ed Rubin,   Lawrence Berkeley National Lab

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Related Genotype: a/a

Description
Mice carrying the human apolipoprotein A-I transgene show a two fold increase in total plasma cholesterol levels and greater than a four fold decrease in the levels of mouse apoAI. Homozygous transgenic mice exhibit reduced susceptibility to diet induced fatty streak lesions. Mice homozygous for the transgenic insert are viable, fertile and normal in size. This human apolipoprotein AI transgene is under the control of its natural promoter. The Jackson Laboratory imported mice derived from the founder line A2 as described in Rubin EM, et al., 1991.

Development
A transgenic construct containing the entire human apolipoprotein A-I gene including the promoter, APOA1, was injected into fertilized C57BL/6 mouse eggs. Founder line A2 was subsequently established.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Amyloidosis, Familial Visceral   (APOA1) Apolipoprotein A-I; APOA1   (APOA1) Hypoalphalipoproteinemia, Primary   (APOA1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tg(APOA1)1Rub/0

        involves: C57BL/6

• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype
  • despite being fed an atherogenic diet, mice exhibit no change in total cholesterol, triglyceride and HDL-cholesterol levels compared to similarly treated wild-type mice   (MGI Ref ID J:128254)
• • decreased circulating triglyceride level   (MGI Ref ID J:121992)
• cardiovascular system phenotype
• decreased susceptibility to atherosclerosis
  • atherosclerotic lesions are 3-fold smaller than in Tg(APOA1)1Rub Tg(AlbLCAT)1Jdm or Tg(APOA1)1Rub Tg(CETP)5203Tall mice and 4-fold smaller than in Tg(AlbLCAT)1Jdm mice   (MGI Ref ID J:128254)
  • the risk of developing atherosclerotic lesions greater than 50th percentile is 4.3-fold lower than in wild-type mice   (MGI Ref ID J:128254)

Tg(APOA1)1Rub/Tg(APOA1)1Rub

        C57BL/6-Tg(APOA1)1Rub/J

• homeostasis/metabolism phenotype
• abnormal circulating interleukin-17 level
  • in bone marrow transplants experiments, mice receiving bone marrow transduced with an Flt3-ITD-expressing retrovirus exhibit less of an increase in plasma IL17 compared with control mice   (MGI Ref ID J:190966)
• abnormal lipid homeostasis
  • HDL particle size has a bimodal distribution with two peaks at 8.5 and 10.5 nm compared to the single peak at 9.9 nm for non-transgenic controls   (MGI Ref ID J:92450)
  • 90% of HDL particles contain human apoA-I instead of endogenous murine apo-AI   (MGI Ref ID J:129704)
  • HDL particle size has a bimodal distribution with two peaks similar to human HDL particles that contain apoA-I   (MGI Ref ID J:129704)
• • abnormal lipid level
    • total APOA1 (mouse and human ) is increased two fold   (MGI Ref ID J:42425)
    • mouse APOA1 is reduced 95%   (MGI Ref ID J:42425)
    • mouse APOA2 is reduced 45%   (MGI Ref ID J:42425)
    • HDL particles include two subsets of larger (10.2-10.8nm) and smaller particles (8.4-8.6nm) as compared to control; these sizes fall with the range for human HDL-2b and HDL-3a, respectively   (MGI Ref ID J:42425)
  • • abnormal circulating HDL cholesterol level
      • in bone marrow transplants experiments, mice receiving bone marrow transduced with an Flt3-ITD-expressing retrovirus exhibit less of a decrease in HDL cholesterol compared with control mice   (MGI Ref ID J:190966)
    • • increased circulating HDL cholesterol level   (MGI Ref ID J:42425)
    • increased circulating cholesterol level
      • HDL cholesterol is increased two fold   (MGI Ref ID J:42425)
    • • increased circulating HDL cholesterol level   (MGI Ref ID J:42425)
• increased cholesterol efflux
  • in macrophages in vitro   (MGI Ref ID J:107390)
• cardiovascular system phenotype
• decreased susceptibility to atherosclerosis
  • reduced susceptibility to diet-induced fatty streak lesions   (MGI Ref ID J:99552)
  • macrophages transplanted into Apoa1^tm1Unc homozygotes or bone marrow transplanted into Apoa1^tm1Unc homozygotes in conjunction with Apoe^tm1Unc bone marrow confers resistance to diet-induced atherosclerosis   (MGI Ref ID J:107390)
  • there is a greater than 40-fold reduction in the mean lesion area found in the aorta of mice fed an atherogenic diet for 36 weeks compared to wild-type mice   (MGI Ref ID J:129704)
• hematopoietic system phenotype
• abnormal hematopoietic system physiology
  • in bone marrow transplants experiments, mice receiving bone marrow transduced with an Flt3-ITD-expressing retrovirus exhibit less of an increase in hematopoietic stem and multipotential progenitor cell (HSPC) mobilization in compared with control mice   (MGI Ref ID J:190966)
• abnormal spleen weight
  • in bone marrow transplants experiments, mice receiving bone marrow transduced with an Flt3-ITD-expressing retrovirus exhibit less of an increase in spleen weight compared with control mice   (MGI Ref ID J:190966)
• decreased hematopoietic stem cell number
  • in bone marrow transplants experiments, mice receiving bone marrow transduced with an Flt3-ITD-expressing retrovirus exhibit less of an increase in LSK cells in the spleen compared with control mice   (MGI Ref ID J:190966)
• increased hematopoietic stem cell number
  • in bone marrow transplants experiments, mice receiving bone marrow transduced with an Flt3-ITD-expressing retrovirus exhibit an increase in LSK cells in the bone marrow compared with control mice   (MGI Ref ID J:190966)
• cellular phenotype
• increased cholesterol efflux
  • in macrophages in vitro   (MGI Ref ID J:107390)
• immune system phenotype
• abnormal circulating interleukin-17 level
  • in bone marrow transplants experiments, mice receiving bone marrow transduced with an Flt3-ITD-expressing retrovirus exhibit less of an increase in plasma IL17 compared with control mice   (MGI Ref ID J:190966)
• abnormal spleen weight
  • in bone marrow transplants experiments, mice receiving bone marrow transduced with an Flt3-ITD-expressing retrovirus exhibit less of an increase in spleen weight compared with control mice   (MGI Ref ID J:190966)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

APOA1 related

Cardiovascular Research
Hypercholesterolemia

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(APOA1)1Rub
Allele Name		transgene insertion 1, Edward M Rubin
Allele Type		Transgenic (random, expressed)
Common Name(s)		Hu apo AI; apoA-I/A-IKO; hA-I; hApoA-I/Tg; hapoA1;
Mutation Made By		Dr. Ed Rubin,   Lawrence Berkeley National Lab
Strain of Origin		C57BL/6
Expressed Gene		APOA1, apolipoprotein A-I, human
Promoter		APOA1, apolipoprotein A-I, human
General Note		Transgenic mice display a two fold increase in total plasma cholesterol levels and greater than a four fold decrease in the levels of mouse APOA1. Two lines were produced, A2 and A16.
Molecular Note		The transgene contains the human apolipoprotein A-I gene including the promoter. [MGI Ref ID J:42425]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(APOA1)1Rub, QPCR
Tg(APOA1)1Rub, Standard PCR
Tg(APOA1)1Rub-QPCR2, QPCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Rubin EM; Ishida BY; Clift SM; Krauss RM. 1991. Expression of human apolipoprotein A-I in transgenic mice results in reduced plasma levels of murine apolipoprotein A-I and the appearance of two new high density lipoprotein size subclasses. Proc Natl Acad Sci U S A 88(2):434-8. [PubMed: 1703299]  [MGI Ref ID J:42425]

Additional References

Ishiguro H; Yoshida H; Major AS; Zhu T; Babaev VR; Linton MF; Fazio S. 2001. Retrovirus-mediated expression of apolipoprotein A-I in the macrophage protects against atherosclerosis in vivo. J Biol Chem 276(39):36742-8. [PubMed: 11477092]  [MGI Ref ID J:71811]

Tg(APOA1)1Rub related

Berti JA; de Faria EC; Oliveira HC. 2005. Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes. Braz J Med Biol Res 38(3):391-8. [PubMed: 15761619]  [MGI Ref ID J:128254]

Chiesa G; Parolini C; Canavesi M; Colombo N; Sirtori CR; Fumagalli R; Franceschini G; Bernini F. 1998. Human apolipoproteins A-I and A-II in cell cholesterol efflux: studies with transgenic mice. Arterioscler Thromb Vasc Biol 18(9):1417-23. [PubMed: 9743230]  [MGI Ref ID J:129136]

Dansky HM; Charlton SA; Barlow CB; Tamminen M; Smith JD; Frank JS; Breslow JL. 1999. Apo A-I inhibits foam cell formation in Apo E-deficient mice after monocyte adherence to endothelium. J Clin Invest 104(1):31-9. [PubMed: 10393696]  [MGI Ref ID J:115306]

Fournier N; Atger V; Paul JP; de la Llera Moya M; Rothblat G; Moatti N. 1999. Fractional efflux and net change in cellular cholesterol content mediated by sera from mice expressing both human apolipoprotein AI and human lecithin:cholesterol acyltransferase genes. Atherosclerosis 147(2):227-35. [PubMed: 10559507]  [MGI Ref ID J:59668]

Francone OL; Gong EL; Ng DS; Fielding CJ; Rubin EM. 1995. Expression of human lecithin-cholesterol acyltransferase in transgenic mice. Effect of human apolipoprotein AI and human apolipoprotein all on plasma lipoprotein cholesterol metabolism. J Clin Invest 96(3):1440-8. [PubMed: 7657816]  [MGI Ref ID J:121992]

Ishiguro H; Yoshida H; Major AS; Zhu T; Babaev VR; Linton MF; Fazio S. 2001. Retrovirus-mediated expression of apolipoprotein A-I in the macrophage protects against atherosclerosis in vivo. J Biol Chem 276(39):36742-8. [PubMed: 11477092]  [MGI Ref ID J:71811]

Jiang X; Francone OL; Bruce C; Milne R; Mar J; Walsh A; Breslow JL; Tall AR. 1996. Increased prebeta-high density lipoprotein, apolipoprotein AI, and phospholipid in mice expressing the human phospholipid transfer protein and human apolipoprotein AI transgenes. J Clin Invest 98(10):2373-80. [PubMed: 8941656]  [MGI Ref ID J:129463]

Komori H; Arai H; Kashima T; Huby T; Kita T; Ueda Y. 2008. Coexpression of CLA-1 and human PDZK1 in murine liver modulates HDL cholesterol metabolism. Arterioscler Thromb Vasc Biol 28(7):1298-303. [PubMed: 18403724]  [MGI Ref ID J:159814]

Lewis TL; Cao D; Lu H; Mans RA; Su YR; Jungbauer L; Linton MF; Fazio S; LaDu MJ; Li L. 2010. Overexpression of human apolipoprotein A-I preserves cognitive function and attenuates neuroinflammation and cerebral amyloid angiopathy in a mouse model of Alzheimer disease. J Biol Chem 285(47):36958-68. [PubMed: 20847045]  [MGI Ref ID J:167024]

Major AS; Dove DE; Ishiguro H; Su YR; Brown AM; Liu L; Carter KJ; Linton MF; Fazio S. 2001. Increased cholesterol efflux in apolipoprotein AI (ApoAI)-producing macrophages as a mechanism for reduced atherosclerosis in ApoAI((-/-)) mice. Arterioscler Thromb Vasc Biol 21(11):1790-5. [PubMed: 11701467]  [MGI Ref ID J:107390]

Masson D; Qatanani M; Sberna AL; Xiao R; Pais de Barros JP; Grober J; Deckert V; Athias A; Gambert P; Lagrost L; Moore DD; Assem M. 2008. Activation of the constitutive androstane receptor decreases HDL in wild-type and human apoA-I transgenic mice. J Lipid Res 49(8):1682-91. [PubMed: 18441373]  [MGI Ref ID J:138452]

Moerland M; Samyn H; van Gent T; Jauhiainen M; Metso J; van Haperen R; Grosveld F; van Tol A; de Crom R. 2007. Atherogenic, enlarged, and dysfunctional HDL in human PLTP/apoA-I double transgenic mice. J Lipid Res 48(12):2622-31. [PubMed: 17761633]  [MGI Ref ID J:129970]

Norata GD; Callegari E; Marchesi M; Chiesa G; Eriksson P; Catapano AL. 2005. High-density lipoproteins induce transforming growth factor-beta2 expression in endothelial cells. Circulation 111(21):2805-11. [PubMed: 15911702]  [MGI Ref ID J:112255]

Norata GD; Marchesi P; Pirillo A; Uboldi P; Chiesa G; Maina V; Garlanda C; Mantovani A; Catapano AL. 2008. Long pentraxin 3, a key component of innate immunity, is modulated by high-density lipoproteins in endothelial cells. Arterioscler Thromb Vasc Biol 28(5):925-31. [PubMed: 18218986]  [MGI Ref ID J:159816]

Paszty C; Maeda N; Verstuyft J; Rubin EM. 1994. Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice. J Clin Invest 94(2):899-903. [PubMed: 8040345]  [MGI Ref ID J:111180]

Rubin EM; Krauss RM; Spangler EA; Verstuyft JG; Clift SM. 1991. Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI. Nature 353(6341):265-7. [PubMed: 1910153]  [MGI Ref ID J:99552]

Schultz JR; Gong EL; McCall MR; Nichols AV; Clift SM; Rubin EM. 1992. Expression of human apolipoprotein A-II and its effect on high density lipoproteins in transgenic mice. J Biol Chem 267(30):21630-6. [PubMed: 1400473]  [MGI Ref ID J:92450]

Schultz JR; Verstuyft JG; Gong EL; Nichols AV; Rubin EM. 1993. Protein composition determines the anti-atherogenic properties of HDL in transgenic mice. Nature 365(6448):762-4. [PubMed: 8413656]  [MGI Ref ID J:129704]

Srivastava RA; He S; Newton RS. 2011. Differential regulation of human apolipoprotein AI and high-density lipoprotein by fenofibrate in hapoAI and hapoAI-CIII-AIV transgenic mice. Biochim Biophys Acta 1811(2):76-83. [PubMed: 21081177]  [MGI Ref ID J:170268]

Su F; Kozak KR; Imaizumi S; Gao F; Amneus MW; Grijalva V; Ng C; Wagner A; Hough G; Farias-Eisner G; Anantharamaiah GM; Van Lenten BJ; Navab M; Fogelman AM; Reddy ST; Farias-Eisner R. 2010. Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides inhibit tumor development in a mouse model of ovarian cancer. Proc Natl Acad Sci U S A 107(46):19997-20002. [PubMed: 21041624]  [MGI Ref ID J:166609]

Terasaka N; Yu S; Yvan-Charvet L; Wang N; Mzhavia N; Langlois R; Pagler T; Li R; Welch CL; Goldberg IJ; Tall AR. 2008. ABCG1 and HDL protect against endothelial dysfunction in mice fed a high-cholesterol diet. J Clin Invest 118(11):3701-13. [PubMed: 18924609]  [MGI Ref ID J:144580]

Theilmeier G; De Geest B; Van Veldhoven PP; Stengel D; Michiels C; Lox M; Landeloos M; Chapman MJ; Ninio E; Collen D; Himpens B; Holvoet P. 2000. HDL-associated PAF-AH reduces endothelial adhesiveness in apoE-/- mice. FASEB J 14(13):2032-9. [PubMed: 11023987]  [MGI Ref ID J:119589]

Tietge UJ; Maugeais C; Lund-Katz S; Grass D; deBeer FC; Rader DJ. 2002. Human secretory phospholipase A2 mediates decreased plasma levels of HDL cholesterol and apoA-I in response to inflammation in human apoA-I transgenic mice. Arterioscler Thromb Vasc Biol 22(7):1213-8. [PubMed: 12117740]  [MGI Ref ID J:107203]

Westerterp M; Gourion-Arsiquaud S; Murphy AJ; Shih A; Cremers S; Levine RL; Tall AR; Yvan-Charvet L. 2012. Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathways. Cell Stem Cell 11(2):195-206. [PubMed: 22862945]  [MGI Ref ID J:190966]

Yvan-Charvet L; Pagler T; Gautier EL; Avagyan S; Siry RL; Han S; Welch CL; Wang N; Randolph GJ; Snoeck HW; Tall AR. 2010. ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science 328(5986):1689-93. [PubMed: 20488992]  [MGI Ref ID J:161310]

Zhang Y; Da Silva JR; Reilly M; Billheimer JT; Rothblat GH; Rader DJ. 2005. Hepatic expression of scavenger receptor class B type I (SR-BI) is a positive regulator of macrophage reverse cholesterol transport in vivo. J Clin Invest 115(10):2870-4. [PubMed: 16200214]  [MGI Ref ID J:101524]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX1

Colony Maintenance

Breeding & Husbandry	This strain is maintained by homozygous sibling matings.
Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06
Breeding Considerations	This strain is a good breeder.
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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