Description

Strain Information

Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Noncarrier x Hemizygote         (Female x Male) Species laboratory mouse Generation F?+N1+ (27-AUG-08)   Donating Investigator Robert Farese, Jr.,   Gladstone Institute UCSF

Description
Mice hemizygous for this LivLE6-DGAT2 transgene are viable and fertile, with human DGAT2 expression directed to the liver by the hepatic promoter/enhancer sequences from the human apolipoprotein E gene. Mice from founder line 24 (referred to as Liv-DGAT2-low) have an approximately 2-fold increase in total hepatic DGAT2 mRNA/protein expression, with no reported overexpression in kidney, brain, or skeletal muscle. As DGAT2 is one of two enzymes that catalyze the final step of triacylglycerol (TG) biosynthesis, transgenic mice develop hepatic steatosis with increased hepatic TG and insulin signaling lipid (diacylglycerol, ceramide and unsaturated Fatty AcylCoA) content. Liv-DGAT2-low mice also exhibit increased transcription of fatty acid synthesis genes (SREBP-1c, fatty acid synthase, and stearoyl CoA desaturase 1). Fasted mice show a 65% decrease in plasma TG, but are not insulin resistant (blood glucose and insulin are similar to wildtype). Liv-DGAT2-low mice challenged with a high-fat diet do not exhibit impaired glucose or insulin tolerance more than that found in control mice. These Liv-DGAT2-low transgenic mice may be useful in studying hepatic steatosis, lipid, glucose, and insulin metabolism, as well as obesity and diabetes.

Of note, these mice may also be useful in conjunction with MCK-DGAT2 transgenic mice (Stock No. 006781) which exhibit DGAT2 overexpression directed to glycolytic striated skeletal muscle.

Development
The LivLE6-DGAT2 transgene was designed with promoter and enhancer sequences of the human apolipoprotein E gene placed upstream of a 1.2 kb human acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2) cDNA sequence. This transgene was microinjected into C57BL/6NHsd fertilized eggs, and the resulting transgenic offspring were bred to C57BL/6NHsd. Founder line 24 (Liv-DGAT2-low) mice were established and maintained by breeding transgenic mice to C57BL/6NHsd for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6NJ (Stock No. 005304) to establish the colony.

Control Information

	Control
	Noncarrier
	005304 C57BL/6NJ	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of APOE

004632	B6.Cg-Tg(GFAP-APOE*2)14Hol Apoetm1Unc/J
004631	B6.Cg-Tg(GFAP-APOE*4)1Hol Apoetm1Unc/J
008408	B6;D2-Tg(APOE-NPC1L1)20Lqyu/J
003285	C57BL/6-Tg(LIPC)6784His/J

View Strains carrying other alleles of APOE     (4 strains)

Strains carrying other alleles of DGAT2

006781

C57BL/6-Tg(Ckm-DGAT2)10Far/J

View Strains carrying other alleles of DGAT2     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tg(APOE-DGAT2)24Far/0

        involves: C57BL/6NHsd

• liver/biliary system phenotype
• enlarged liver (MGI Ref ID J:124005)
  • resulting from steatosis; liver weight to body weight ratio (0.047) is higher than in wild-type mice
• hepatic steatosis (MGI Ref ID J:124005)
  • steatosis exhibited by increase in size and paleness of livers
• pale liver (MGI Ref ID J:124005)
  • due to lipid deposits resulting from steatosis
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:124005)
  • food intake and body composition are not altered compared to wild-type animals
  • plasma levels of adipokines and inflammatory cytokines are similar to wild-type mice
  • blood glucose and insulin levels are similar to wild-type mice; transgenic mice do not display differences in glucose or insulin tolerance so mice are not insulin resistant
  • following feeding of a high-fat diet for 16 weeks, transgenic and control mice show similar degree of impairment of glucose tolerance and insulin resistance
• abnormal circulating enzyme level (MGI Ref ID J:124005)
  • plasma transaminase levels are slightly elevated relative to wild-type
• abnormal lipid level (MGI Ref ID J:124005)
  • tissue content of diacylglycerol and ceramides are increased in liver; ; however, levels in skeletal muscle are not altered
• abnormal fatty acid level (MGI Ref ID J:124005)
  • content of unsaturated long-chain fatty acyl-CoAs are increased in the liver, but levels of saturated long-chain fatty acyl-CoAs are not
• decreased circulating free fatty acid level (MGI Ref ID J:124005)
  • plasma levels are slightly decreased relative to wild-type
• decreased circulating triglyceride level (MGI Ref ID J:124005)
  • plasma triglyceride levels in fasted mice are decreased by >65% relative to controls
• increased triglyceride level (MGI Ref ID J:124005)
  • triglyceride content is increased ~5-fold over wild-type

View Research Applications

Research Applications

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

Cardiovascular Research
Hypertriglyceridemia
Other (altered fat metabolism)
Other (altered lipoprotein profile)

Internal/Organ Research
Liver Defects

Metabolism Research
Lipid Metabolism

Research Tools
Cardiovascular Research
Diabetes and Obesity Research
Internal/Organ Research
Metabolism Research

APOE related

Mouse/Human Gene Homologs
Alzheimer's

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(APOE-DGAT2)24Far
Allele Name		transgene insertion 24, Bob Farese
Allele Type		Transgenic (random, expressed)
Common Name(s)		Liv-DGAT2-low; LivLe6-DGAT2 (low);
Mutation Made By		Mara Monetti,   Gladstone Institute UCSF
Strain of Origin		C57BL/6NHsd
Expressed Gene		DGAT2, diacylglycerol O-acyltransferase homolog 2 (mouse), human
Promoter		APOE, apolipoprotein E, human
Molecular Note		The LivLE6-DGAT2 transgene was designed with promoter and enhancer sequences of the human apolipoprotein E gene placed upstream of a 1.2 kb human acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2) cDNA sequence. This transgene was microinjected into C57BL/6NHsd fertilized eggs, and the resulting transgenic offspring were bred to C57BL/6NHsd. Mice from founder line 24 (referred to as Liv-DGAT2-low) have an approximately 2-fold increase in total hepatic DGAT2 mRNA/protein expression, with no reported overexpression in kidney, brain, or skeletal muscle. [MGI Ref ID J:124005]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(APOE-DGAT2)24Far, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Monetti M; Levin MC; Watt MJ; Sajan MP; Marmor S; Hubbard BK; Stevens RD; Bain JR; Newgard CB; Farese RV Sr; Hevener AL; Farese RV Jr. 2007. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab 6(1):69-78. [PubMed: 17618857]  [MGI Ref ID J:124005]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, transgenic mice can be bred to wildtype siblings. Alternatively, transgenic mice may be bred together, although a homozygous phenotype is not yet characterized (Jul-2007).
Mating System	Noncarrier 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
	005304 C57BL/6NJ	(approximate)
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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Terms of Use

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fax:	207-288-6655

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