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

Stock number: 007744
Research areas: Cardiovascular Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

These Liv-DGAT2-low transgenic mice may be useful in studying hepatic steatosis, lipid, glucose, and insulin metabolism, as well as obesity and diabetes.

Detailed 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.

Allele

Symbol: Tg(APOE-DGAT2)24Far
Name: transgene insertion 24, Bob Farese
MGI accession ID: MGI:3720356
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(APOE-DGAT2)24Far
Marker name: transgene insertion 24, Bob Farese
Chromosome: UN
Strain of origin: C57BL/6NHsd
Expressed genes: DGAT2,diacylglycerol O-acyltransferase 2,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.