B6;SJL-Tg(Mt1-LDLR)93-4Reh/AgnJ

Stock number: 008850
Research areas: Cardiovascular Research, Internal/Organ Research, Metabolism Research, Neurobiology Research, Research Tools

Description

These hLDLRTg mice exhibit human low density lipoprotein receptor (hLDLR) expression controlled by the mouse metallothionein 1 gene (Mt1) promoter sequences and may be useful for studying the role of apolipoproteins and their receptors, lipid transport and lipoprotein metabolism in a wide variety of disease (including atherosclerosis, Alzheimer's disease, and hepatitis C).

Detailed description

Mice hemizygous for this MMT-I-hLDLR transgene (hLDLRTg mice) are viable and fertile, with human low density lipoprotein receptor (hLDLR) expression controlled by the mouse metallothionein 1 gene (Mt1) promoter sequences. The donating investigator reports that homozygous mice are not viable. Expression of hLDLR mRNA is highest in liver, moderate in kidney, small intestine, and heart, and lowest in brain and pancreas. Treatment with cadmium sulfate (CdSO4) stimulates transcription from the metallothionein promoter and results in higher levels of hLDLR expression. This overexpression of functional LDLR in transgenic mice results in greatly increased clearance of LDLR ligands (LDL, apoprotein B-100 and apoprotein E) from plasma when compared to wild-type mice. These hLDLRTg mice may be useful for studying the role of apolipoproteins and their receptors, lipid transport and lipoprotein metabolism in a wide variety of disease (including atherosclerosis, Alzheimer's disease, and hepatitis C).

Development

Transgenic mice were created in the laboratory of Dr. Robert E Hammer (University of Texas Southwestern Medical Center). The MMT-I-hLDLR transgene was designed with a 1.7 kb fragment of mouse metallothionein 1 gene (Mt1) promoter, a 2.6 kb cDNA of the human low density lipoprotein receptor (hLDLR) complete coding region (and 27 basepairs of 5' UTR), and the transcription termination signal from the human growth hormone gene. This transgene was microinjected into the male pronuclei of fertilized (C57/SJL)F2 hybrid mouse eggs, Founder mouse 93-4, with high hLDLR expression in the liver, was bred to establish the colony. Only offspring with approximately three copies of the transgene integrated at a single site were shown to express hLDLR mRNA, and these mice were used to propagate the colony. MMT-I-hLDLR transgenic mice on a mixed B6;SJL genetic background were then sent to Dr. Vincent Agnello (Veterans Affairs Medical Center). There, the colony was maintained by breeding transgenic males with C57BL/6NCrl females for approximately 12 generations, and then to B6SJLF1/J mice (Stock No. 100012) for approximately four generations prior to arrival at The Jackson Laboratory. Upon arrival, transgenic mice were bred with B6SJLF1/J mice (Stock No. 100012) for at least one generation to establish the colony.

Allele

Symbol: Tg(Mt1-LDLR)93-4Reh
Name: transgene insertion 93-4, Robert E Hammer
MGI accession ID: MGI:3848828
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Mt1-LDLR)93-4Reh
Marker name: transgene insertion 93-4, Robert E Hammer
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F2
Expressed genes: LDLR,low density lipoprotein receptor,human
Molecular note: Transgenic mice were created in the laboratory of Dr. Robert E Hammer (University of Texas Southwestern Medical Center). The MMT-I-hLDLR transgene was designed with a 1.7 kb fragment of mouse metallothionein 1 gene (Mt1) promoter, a 2.6 kb cDNA of the human low density lipoprotein receptor (hLDLR) complete coding region (and 27 basepairs of 5' UTR), and the transcription termination signal from the human growth hormone gene. This transgene was microinjected into the male pronuclei of fertilized (C57/SJL)F2 hybrid mouse eggs, Founder mouse 93-4, with high hLDLR expression in the liver, was bred to establish the colony. These mice have 3 copies of the transgene inserted at a single site and express human LDLR mRNA.