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).
Vincent Agnello, Veteran Affairs Medical Center
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
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).
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.
Expressed Gene | LDLR, low density lipoprotein receptor, human |
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Site of Expression |
Allele Name | transgene insertion 93-4, Robert E Hammer |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | hLDLRTg; mMT-I-hLDLR-hGH |
Gene Symbol and Name | Tg(Mt1-LDLR)93-4Reh, transgene insertion 93-4, Robert E Hammer |
Gene Synonym(s) | |
Promoter | Mt1, metallothionein 1, mouse, laboratory |
Expressed Gene | LDLR, low density lipoprotein receptor, human |
Strain of Origin | (C57BL/6 x SJL)F2 |
Chromosome | UN |
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. |
Mutations Made By | Robert Hammer, UT Southwestern Medical Center at Dallas |
When maintaining a live colony, hemizygous mice may be bred to noncarrier (wildtype) siblings or to B6SJLF1/J mice (Stock No. 100012). The donating investigator reports that homozygous mice are not viable.
When using the B6;SJL-Tg(Mt1-LDLR)93-4Reh/AgnJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #008850 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Hemizygous or Non carrier for Tg(Mt1-LDLR)93-4Reh |
Frozen Mouse Embryo | B6;SJL-Tg(Mt1-LDLR)93-4Reh/AgnJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;SJL-Tg(Mt1-LDLR)93-4Reh/AgnJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;SJL-Tg(Mt1-LDLR)93-4Reh/AgnJ Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6;SJL-Tg(Mt1-LDLR)93-4Reh/AgnJ Frozen Embryo | $3373.50 |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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