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Genes & Alleles

Ckm;   DGAT2;   Tg(Ckm-DGAT2)10Far;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Coisogenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Transgenic Mating System Noncarrier x Hemizygote         (Female x Male) Species laboratory mouse Donating Investigator Robert Farese, Jr.,   Gladstone Institute UCSF Generation ?+N1+ (12-MAY-08)

Strain Description
Mice hemizygous for this MCK-DGAT2 transgene are viable and fertile. Under direction of the mouse muscle creatine kinase (MCK) promoter, these mice overexpress human acyl CoA:diacylglycerol acyltransferase 2 (DGAT2) in striated skeletal muscles, specifically glycolytic (rather than oxidative) muscle. DGAT2 overexpression leads to increased lipid deposition (triacylglycerol, ceramide, and fatty acyl CoA) in glycolytic muscle. This lipid accumulation leads to impaired insulin signaling (insulin resistance), glucose uptake, and glucose tolerance in this tissue, as well as whole-body glucose intolerance. These MCK-DGAT2 transgenic mice may be useful in studying lipid accumulation in skeletal muscle, insulin and glucose metabolism, obesity, and type 2 diabetes.

Of note, these mice may also be useful in conjunction with Liv-DGAT2-low transgenic mice (Stock No. 007744) which exhibit DGAT2 overexpression directed to hepatic tissue.

Strain Development
The MCK-DGAT2 transgene was designed with 4 kb of the mouse muscle creatine kinase (MCK) promoter sequence placed upstream of a 1.2 kb human acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2) cDNA sequence, followed by a 2.2 kb human growth hormone minigene (providing the polyA signal). The transgene was microinjected into C57BL/6NHsd fertilized eggs and the resulting transgenic offspring were bred to C57BL/6NHsd. Founder line 10 mice were established and maintained by breeding transgenic mice to wildtype littermates for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice may have been bred with C57BL/6J to establish the colony.

Mammalian Phenotype Terms assigned by genotype Tg(Ckm-DGAT2)10Far/0         involves: C57BL/6NHsd homeostasis/metabolism phenotype abnormal glucose homeostasis (MGI Ref ID J:129495) basal uptake of 2-deoxyglucose in glycolytic and oxidative muscle trend higher in transgenic mice compared to wild-type impaired glucose tolerance (MGI Ref ID J:129495) tolerance is impaired at 15, 30, and 60 minutes after glucose challenge in 3-month old males insulin resistance (MGI Ref ID J:129495) in response to insulin, 2-deoxyglucose uptake is impaired in glycolytic muscle, while uptake is stimulated ~2-fold in wild-type glycolytic muscle by insulin 3-month old male mice show impaired insulin tolerance with higher glucose levels 60 minutes after insulin injection compared to wild-type abnormal lipid level (MGI Ref ID J:129495) at 3 months in males, diglyceride levels are 42% lower in glycolytic muscle compared to wild-type; ceramide levels are 63% higher and some saturated acyl CoA species are elevated also whereas levels in oxidative muscle are similar in transgenic and wild-type mice by 6 months of age, lipid content in glycolytic muscle increase to similar levels in both genotypes increased triglyceride level (MGI Ref ID J:129495) in 3 month-old male mice, transgene expression increases triglyceride level in glycolytic muscle 1.8-fold, while levels in oxidative muscle, white adipose tissue and liver are similar to wild-type levels by 6 months of age, triglyceride content in glycolytic muscle increase to similar levels in both genotypes

Gene & Allele Details

Allele Symbol		Tg(Ckm-DGAT2)10Far
Allele Name		transgene insertion 10, Bob Farese
Common Name(s)		MCK-DGAT2;
Mutation Made By		Malin Levin,   The Sahlgenska Academy, Göteborg Univ
Strain of Origin		C57BL/6NHsd
Expressed Gene		DGAT2, diacylglycerol O-acyltransferase homolog 2 (mouse), human
Promoter		Ckm, creatine kinase, muscle, mouse, laboratory
Molecular Note		The targeting construct was designed with 4 kb of the mouse muscle creatine kinase (MCK) promoter sequence placed upstream of a 1.2 kb human acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2) cDNA sequence, followed by a 2.2 kb human growth hormone minigene (providing the polyA signal). The transgene was microinjected into C57BL/6NHsd fertilized eggs and the resulting transgenic offspring were bred to C57BL/6NHsd. Founder line 10 mice were established. [MGI Ref ID J:129495]

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

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).
Diet Information	LabDiet® 5K52/5K67

Related Strains

Strains carrying other alleles of Ckm

006475	B6.FVB(129S4)-Tg(Ckmm-cre)5Khn/J
006405	FVB-Tg(Ckmm-cre)5Khn/J

View Strains carrying other alleles of Ckm     (2 strains)

Strains carrying other alleles of DGAT2

007744

C57BL/6-Tg(APOE-DGAT2)24Far/J

View Strains carrying other alleles of DGAT2     (1 strain)

Animal Health Reports

Room Number           AX11

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)

Diabetes and Obesity Research
Hyperglycemia
Impaired Insulin Processing
Insulin Resistance
Type 2 Diabetes (NIDDM)

Metabolism Research
Lipid Metabolism

Research Tools
Diabetes and Obesity Research
Metabolism Research

References

Selected Reference(s)

Levin MC; Monetti M; Watt MJ; Sajan MP; Stevens RD; Bain JR; Newgard CB; Farese RV Sr; Farese RV Jr. 2007. Increased lipid accumulation and insulin resistance in transgenic mice expressing DGAT2 in glycolytic (type II) muscle. Am J Physiol Endocrinol Metab 293(6):E1772-81. [PubMed: 17940217]  [MGI Ref ID J:129495]

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Price and Supply Information

Strain Name:	C57BL/6-Tg(Ckm-DGAT2)10Far/J
Stock Number:	006781

Price Details

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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.
Licensing	See General Terms and Conditions below
Control Information	View Control Information in Strain Details.

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View JAX^® Mice & Services Conditions 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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