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

Stock number: 006781
Research areas: Cardiovascular Research, Diabetes and Obesity Research, Metabolism Research, Research Tools

Description

These MCK-DGAT2 transgenic mice may be useful in studying lipid accumulation in skeletal muscle, insulin and glucose metabolism, obesity, and type 2 diabetes.

Detailed 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.

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.

Allele

Symbol: Tg(Ckm-DGAT2)10Far
Name: transgene insertion 10, Bob Farese
MGI accession ID: MGI:3717406
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Ckm-DGAT2)10Far
Marker name: transgene insertion 10, Bob Farese
Chromosome: UN
Strain of origin: C57BL/6NHsd
Expressed genes: DGAT2,diacylglycerol O-acyltransferase 2,human
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.