Description

Strain Information

Type Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N13   Donating Investigator Aldons Lusis,   University of California at Los Angeles

Description
This strain carryies the mouse apolipoprotein A-II transgene. Fasting plasma APOA2 concentrations in transgenic mice are on average about 3-fold higher than normal wildtype siblings with males showing a 1.5-fold higher level than females. ApoA-I concentraions are normal. These mice show a 3-fold increase in plasma triglyceride levels, as well as a predisposition to atherosclerotic fatty streak lesions even on a low fat diet.

Control Information

	Control
	Noncarrier female
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Apoa2

006258

B6;129S4-Apoa2tm1Bres/J

View Strains carrying other alleles of Apoa2     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Tg(Apoa2)1Lus/?

        involves: C57BL/6J * DBA/2

• homeostasis/metabolism phenotype
• abnormal lipid homeostasis (MGI Ref ID J:92454)
  • fasting plasma levels of apolioprotein-2 (apoA-II) are 3 fold higher than in non-transgenic controls
  • fasting levels of apoA-II are 1.5 higher in male transgenic mice than in female transgenic mice
  • the ratio of plasma levels of apoA-II to apoA-I averages 2- to 3- fold higher than in non-transgenic controls
  • size of HDL and LDL complexes in the blood are larger than in controls and are enriched for apoA-II protein
  • apo-E protein is found only in LDL complexes and not HDL complexes
  • plasma levels of apolioprotein-2 (apoA-II) are 2- to 3-fold higher on a chow diet than in non-transgenic controls
  • levels of apoA-II are 1.5 higher on a chow diet in male transgenic mice than in female transgenic mice
  • the ratio of plasma levels of apoA-II to apoA-I averages 2- to 3- fold higher on a chow diet than in non-transgenic controls
  • size of HDL complexes in the blood are larger than in controls
  • a complex rich in cholesteryl-ester containing Apo-AII and Apo-E and having a size in between LDL and HDL complexes is found in the sera of transgenic mice
  • the amounts of this intermediate-sized complex increases with an atherogenic diet
• increased circulating cholesterol level (MGI Ref ID J:92454)
  • total circulating cholesterol levels are elevated more than 2-fold
  • total circulating cholesterol levels are elevated more than 2-fold on a chow diet
  • cholesterol levels remain elevated compared to control mice when both are fed an artherogenic diet
• increased circulating HDL cholesterol level (MGI Ref ID J:92454)
  • level of HDL- cholesterol are 2-fold higher for both males and females compared to non-transgenic controls
  • level of HDL- cholesterol are 2-fold higher on a chow diet for both males and females compared to non-transgenic controls
  • cholesterol levels remain elevated compared to control mice when both are fed an artherogenic diet
• increased circulating LDL cholesterol level (MGI Ref ID J:92454)
  • VLDL/LDL cholesterol levels are 113 and 78 mg/dl for male and female mice respectively, compared to 33 mg/dl for both sexes in non-transgenic mice
• increased circulating VLDL cholesterol level (MGI Ref ID J:92454)
  • VLDL/LDL cholesterol levels are 113 and 78 mg/dl for male and female mice respectively, compared to 33 mg/dl for both sexes in non-transgenic mice
• increased circulating triglyceride level (MGI Ref ID J:92454)
  • total plasma triglyceride levels are 2- to 3-fold higher than in non-transgenic mice
• cardiovascular system phenotype
• atherosclerotic lesions (MGI Ref ID J:127063)
  • mice develop atherosclerotic lesions with a mean size of 2020 micrometers² by 4- to 6-months of age
  • lesions consist of fatty streaks with subendothelial accumulations of lipid and foam cells
  • lesions resemble those that occur in C57BL/6J mice fed a high fat, high cholesterol diet
  • male but not female mice maintained on a atherogenic diet for 11 to 12 weeks have an increased lesion size compared to sex-matched non-transgenic controls

View Research Applications

Research Applications

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

Cardiovascular Research
Atherosclerosis
Hypertriglyceridemia

Diabetes and Obesity Research
Hyperinsulinemia (males)
Insulin Resistance (males)

Internal/Organ Research
Adipose Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(Apoa2)1Lus
Allele Name		transgene insertion 1, Aldons J Lusis
Allele Type		Transgenic (random, expressed)
Mutation Made By		Aldons Lusis,   University of California at Los Angeles
Strain of Origin		(C57BL/6J x DBA/2J)F1 x C57BL/6J
Expressed Gene		Apoa2, apolipoprotein A-II, mouse, laboratory
Promoter		Apoa2, apolipoprotein A-II, mouse, laboratory
Molecular Note		The transgene contains mouse apolipoprotein A-II sequence from Swiss 3T3 cells with 4.5 kb of upstream sequence and 8.5 kb of downstream sequence. About 10 copies of the transgene integrated into the genome. The apoA-II expressed from the Swiss 3T3 cell genomic clone carries a more basic apoA-II allele (found among many inbred strains of mice) than the C57BL/6J apoA-II allele. Expression of the transgene in the liver was 4-fold higher than endogenous gene expression. [MGI Ref ID J:92454]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Hedrick CC; Castellani LW; Warden CH; Puppione DL; Lusis AJ. 1993. Influence of mouse apolipoprotein A-II on plasma lipoproteins in transgenic mice. J Biol Chem 268(27):20676-82. [PubMed: 8376417]  [MGI Ref ID J:92454]

Additional References

Tg(Apoa2)1Lus related

Castellani LW; Goto AM; Lusis AJ. 2001. Studies with apolipoprotein A-II transgenic mice indicate a role for HDLs in adiposity and insulin resistance. Diabetes 50(3):643-51. [PubMed: 11246886]  [MGI Ref ID J:67748]

Castellani LW; Nguyen CN; Charugundla S; Weinstein MM; Doan CX; Blaner WS; Wongsiriroj N; Lusis AJ. 2008. Apolipoprotein AII is a regulator of very low density lipoprotein metabolism and insulin resistance. J Biol Chem 283(17):11633-44. [PubMed: 18160395]  [MGI Ref ID J:136532]

Hedrick CC; Castellani LW; Wong H; Lusis AJ. 2001. In vivo interactions of apoA-II, apoA-I, and hepatic lipase contributing to HDL structure and antiatherogenic functions. J Lipid Res 42(4):563-70. [PubMed: 11290828]  [MGI Ref ID J:124753]

Sun Y; Wang N; Tall AR. 1999. Regulation of adrenal scavenger receptor-BI expression by ACTH and cellular cholesterol pools. J Lipid Res 40(10):1799-805. [PubMed: 10508199]  [MGI Ref ID J:120424]

Warden CH; Hedrick CC; Qiao JH; Castellani LW; Lusis AJ. 1993. Atherosclerosis in transgenic mice overexpressing apolipoprotein A-II. Science 261(5120):469-72. [PubMed: 8332912]  [MGI Ref ID J:127063]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. 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
	Noncarrier female
	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

See Terms of Use

The Jackson Laboratory's Genotype Promise

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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Ordering and Purchasing Information

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Fax: 207.288.6150
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Contact information

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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