These RenTgMK mice may be useful in studying the effects of genetically clamped renin (and angiotensin II) on hypertension, diabetic nephropathy, albuninurea, nephrosclerosis, and other aspects of the renin–angiotensin system (RAS).
Dr. Thomas M Coffman, Duke University Medical Center (AMDCC)
Mice heterozygous for the RenTgMK transgene are viable and fertile. The RenTgMK transgene contains a liver-specific albumin promoter/enhancer controlling the expression of a synthetic renin gene (engineered to allow efficient cleavage and secretion of the prorenin transgene product by the liver). This, and because the transgene was targeted to the apolipoprotein locus on Chromosome 9, results in active renin secretion from the liver independently of renal or other homeostatic cardiovascular control mechanisms (i.e. genetically clamped). RenTgMK heterozygotes have high ectopic levels of active mouse renin in the liver and elevated plasma levels of prorenin and active renin. Heterozygous mice display significantly elevated blood pressure, enhanced thirst, high urine output, proteinuria, and kidney damage. Because active renin overexpression results in increased circulating levels of angiotensin II (Ang II), heterozygotes also exhibit cardiac hypertrophy and 50% male mortality between 6-8 months of age. These RenTgMK mice may be useful in studying the effects of genetically clamped renin (and angiotensin II) on hypertension, diabetic nephropathy, albuninurea, nephrosclerosis, and other aspects of the renin angiotensin system (RAS).
A targeting construct was designed to insert a single copy of the RenTgMK transgene into the apolipoprotein locus between the Apoa1 and Apoc3 genes on Chromosome 9. The RenTgMK transgene contains (from 5' to 3') a neomycin resistance cassette, a liver-specific mouse albumin promoter/enhancer sequence (with a 20-bp oligonucleotide insert in the 5' untranslated region (UTR) to increase its length), a synthetic mouse renin cDNA (with a c-myc epitope tag at the 3' end), and a rabbit beta-globin 3' UTR. The synthetic renin cDNA is designed with portions of the Ren-2 (Ren2) and Ren-1d (Ren1) genes to allow efficient processing from prorenin to renin in hepatic or other cells by the ubiquitous enzyme furin. The targeting construct was introduced into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. The donating investigator reports that chimeric males were bred to "129SvEv" females and then maintained on a 129S6/SvEvTac background by Dr. Oliver Smithies and Dr. Nobuyo N. Maeda (University of North Carolina). In 2002, these RenTgMK were sent to Thomas M. Coffman (Duke University) and then backcrossed to 129S6/SvEvTac for at least 11 generations prior to arrival at The Jackson Laboratory.
|Expressed Gene||Ren1, renin 1 structural, mouse, laboratory|
|Site of Expression|
|Allele Name||transgene insertion 2, University of North Carolina|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Allele Synonym(s)||RenTgMK; Tg(Alb1-Ren)1Smi|
|Gene Symbol and Name||Tg(Alb1-Ren)2Unc, transgene insertion 2, University of North Carolina|
|Promoter||Alb, albumin, mouse, laboratory|
|Expressed Gene||Ren1, renin 1 structural, mouse, laboratory|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A single copy of a transgene consisting of a liver specific albumin promoter, a 20 bp insert in the 5' UTR to increase length, a synthetic mouse renin cDNA, and a rabbit beta-globin 3' UTR was inserted into the apolipoprotein locus between the Apoa1 and Apoc3 genes.|
|Mutations Made By|| |
Dr. Oliver Smithies, University of North Carolina at Chapel Hill
When maintaining a live colony, hemizygous (heterozygous) mice can be bred with wildtype littermates.
When using the 129S/SvEv-Tg(Alb1-Ren)2Unc/CofJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #007853 in your Materials and Methods section.
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