Description

Strain Information

Type Mutant Stock; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Hemizygote         (Female x Male) Species laboratory mouse Generation ?+F0 (28-DEC-07)   Donating Investigator Jan Breslow,   Rockefeller University

Description
Mice hemizygous for this "human apo CIII" transgene are viable and fertile. This high expressor founder line (3703) exhibits transgene expression primarily in the liver with some intestinal expression as well. Hemizygous mice have severe plasma hypertriglyceridemia and significantly increased plasma cholesterol. However, resistance to insulin-mediated glucose uptake or hyperinsulinemia are not observed. This high expressor human apo CIII transgenic strain may be useful in studying lipid metabolism, very low density lipoproteins (VLDL), hypertriglyceridemia, coronary heart disease, and/or atherosclerosis.

Development
A transgenic construct containing the human apolipoprotein C-III gene (including 2.5 kb 5' and 1.1 kb 3' flanking sequences) was injected into the male pronucleus of fertilized eggs (both from (C57BL/6J x CBA/J)F1 mice). The resulting animals were bred to (C57BL/6J x CBA/J)F1 to establish founder line 3707. Transgenic mice were bred to wildtype siblings for many generations prior to arrival at The Jackson Laboratory. The donating investigator reports that physical location of transgene insertion(s) are unknown, but given the high expression of the transgene, multiple copies are likely.

Control Information

	Control
	Noncarrier
	100011 B6CBAF1/J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tg(APOC3)3707Bres/0

        involves: C57BL/6J * CBA/J

• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:119638)
  • the mean fasting plasma glucose concentration is essentially identical in transgenic mice and littermate controls
  • the mean fasting plasma insulin concentration is essentially identical in transgenic mice and littermate controls
  • insulin-mediated glucose uptake does not differ between transgenic mice and littermate controls, based on their attaining similar steady-state plasma glucose (SSPG) and steady-state plasma insulin (SSPI) levels following co-infusion of glucose (14.5 mg/min per g body weight) and insulin (0.2 ng/min per gram body weight)
• increased circulating cholesterol level (MGI Ref ID J:119638)
  • the mean fasting cholesterol is significantly higher in 7-8-month old transgenic mice (3.5 +/- 0.2 mmol/l) than in littermate controls (2.4 +/- mmol/l) (P<0.001)
• increased circulating triglyceride level (MGI Ref ID J:119638)
  • the mean fasting plasma triglyceride concentration is considerably higher in 7-8-month old transgenic mice (11.8 +/- 0.2 mmol/l) than in littermate controls (1.1 +/- 0.1 mmol/l) (P<0.001)
• adipose tissue phenotype
• *normal* adipose tissue phenotype (MGI Ref ID J:119638)
  • epididymal fat pad adipocytes isolated from transgenic and control mice exhibit similar glucose transport rates at a maximal insulin concentration (Vmax)
  • the insulin concentration inducing half-maximal glucose transport rate (ED50) is similar in epididymal fat pad adipocytes isolated from transgenic and control mice
  • isoproterenol-induced lipolysis, measured by glycerol release, is essentially identical in transgenic and control epididymal fat pad adipocytes over a dose range of 10^-9-10^-6
  • insulin inhibition of isoproterenol-induced lipolysis, as measured by glycerol release, is essentially identical in transgenic and control epididymal fat pad adipocytes

View Research Applications

Research Applications

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

Cardiovascular Research
Atherosclerosis
Hypercholesterolemia
Hypertriglyceridemia
Other (altered lipoprotein profile)

Diabetes and Obesity Research
Obesity Without Diabetes

Metabolism Research
Lipid Metabolism

Research Tools
Cardiovascular Research
Diabetes and Obesity Research
Metabolism Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(APOC3)3707Bres
Allele Name		transgene insertion 3707, Jan L Breslow
Allele Type		Transgenic (random, expressed)
Common Name(s)		HuCIII Tg;
Mutation Made By		Jan Breslow,   Rockefeller University
Strain of Origin		(C57BL/6J x CBA/J)F1
Expressed Gene		APOC3, apolipoprotein C-III, human
Promoter		APOC3, apolipoprotein C-III, human
Molecular Note		Male pronuclei of fertilized oocytes were microinjected with a transgenic construct comprising the human apolipoprotein C-III gene, including 2.5 kb of 5' and 1.1 kb of 3' flanking sequence. Mice of this line express the transgene at high levels in the liver and secondarily in the intestine. [MGI Ref ID J:81184]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(APOC3)3707Bres, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Reaven GM; Mondon CE; Chen YD; Breslow JL. 1994. Hypertriglyceridemic mice transgenic for the human apolipoprotein C-III gene are neither insulin resistant nor hyperinsulinemic. J Lipid Res 35(5):820-4. [PubMed: 8071604]  [MGI Ref ID J:119638]

Additional References

Tg(APOC3)3707Bres related

Ito Y; Azrolan N; O'Connell A; Walsh A; Breslow JL. 1990. Hypertriglyceridemia as a result of human apo CIII gene expression in transgenic mice. Science 249(4970):790-3. [PubMed: 2167514]  [MGI Ref ID J:81184]

Masucci-Magoulas L; Goldberg IJ; Bisgaier CL; Serajuddin H; Francone OL ; Breslow JL ; Tall AR. 1997. A mouse model with features of familial combined hyperlipidemia. Science 275(5298):391-4. [PubMed: 8994037]  [MGI Ref ID J:37861]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, hemizygous mice are bred to wildtype siblings or to B6CBAF1/J (Stock No. 100011).
Mating System	+/+ sibling x Hemizygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Noncarrier
	100011 B6CBAF1/J
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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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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