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) Species laboratory mouse Generation F?+39 (20-DEC-06)   Donating Investigator Ed Rubin,   Lawrence Berkeley National Lab

Appearance
black
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

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

        C57BL/6-Tg(APOA1)1Rub/J

• homeostasis/metabolism phenotype
• abnormal lipid homeostasis (MGI Ref ID J:92450)
  • 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
  • 90% of HDL particles contain human apoA-I instead of endogenous murine apo-AI
  • HDL particle size has a bimodal distribution with two peaks similar to human HDL particles that contain apoA-I
• abnormal lipid level (MGI Ref ID J:42425)
  • total APOA1 (mouse and human ) is increased two fold
  • mouse APOA1 is reduced 95%
  • mouse APOA2 is reduced 45%
  • 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
• increased circulating cholesterol level (MGI Ref ID J:42425)
  • HDL cholesterol is increased two fold
• increased circulating HDL cholesterol level (MGI Ref ID J:42425)
• increased cholesterol efflux (MGI Ref ID J:107390)
  • in macrophages in vitro
• cardiovascular system phenotype
• decreased susceptibility to atherosclerosis (MGI Ref ID J:99552)
  • reduced susceptibility to diet-induced fatty streak lesions
  • 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
  • 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
• cellular phenotype
• increased cholesterol efflux (MGI Ref ID J:107390)
  • in macrophages in vitro

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

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;
Mutation Made By		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, SEP QPCR, vers. 3
Tg(APOA1)1Rub, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

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]

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]

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]

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]

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)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply	Level 3. Up to 50 mice. Larger quantities or custom orders arranged upon request.
Supply Notes	Shipped at a specific age in weeks. Mice at a precise age in days, littermates and retired breeders are also available. Strains that must be genotyped are not available until five to seven weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
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.

General Terms and Conditions

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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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