Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Dr. Thomas M Coffman,   Duke University Medical Center (AMDCC)

Description
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).

Development
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-1^d (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.

Control Information

	Control
	Noncarrier
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Alb1

016832	B6.FVB(129)-Tg(Alb1-cre)1Dlr/J
002226	C57BL/6J-Tg(Alb1HBV)44Bri/J
016833	FVB(Cg)-Tg(Alb1-cre)1Dlr/J

View Strains carrying other alleles of Alb1     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on transgenic expression of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Hyperuricemic Nephropathy, Familial Juvenile, 2; HNFJ2   (REN) Renal Tubular Dysgenesis; RTD   (REN)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tg(Alb1-Ren)2Unc/?

        129S6/SvEvTac-Tg(Alb1-Ren)2Unc

• cardiovascular system phenotype
• increased systemic arterial blood pressure
  • 145+/-8 mmHg compared to 108+/-9 mmHg in wild-type mice   (MGI Ref ID J:125933)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Tg(Alb1-Ren)2Unc/0

        involves: 129S6/SvEvTac * C57BL/6

• mortality/aging
• premature death
  • about 60% of transgenic males die suddenly between 6 and 8 months of age   (MGI Ref ID J:88650)
• behavior/neurological phenotype
• polydipsia
  • transgenic mice drink significantly more than non-transgenic mice   (MGI Ref ID J:89252)
• cardiovascular system phenotype
• cardiac hypertrophy
  • transgenic mice have: increased left ventricle/body weight ratios; increased cardiac myocyte cross-sectional area; generalized fibrosis; decreased left ventricular end systolic dimension coupled with increased cardiac function, indicating that these mice have concentric hypertrophy, without ventricular dilation or overt heart failure   (MGI Ref ID J:88650)
• decreased heart rate
  • in mice that die prematurely a prolonged and progressive bradycardia is seen   (MGI Ref ID J:88650)
  • transgenics show a significant decrease in heart rate variability compared to wild-type mice   (MGI Ref ID J:88650)
• hypertension
  • transgenic mice have blood pressures more than 25 mmHg higher than wild-type mice   (MGI Ref ID J:89252)
  • administration of an angiotensin II receptor antagonist lowered blood pressure in transgenic mice down to that seen in wild-type mice   (MGI Ref ID J:89252)
  • transgenic mice have blood pressures more than 25 mmHg higher than wild-type mice   (MGI Ref ID J:88650)
• homeostasis/metabolism phenotype
• albuminuria
  • urine protein/creatinine ratios are elevated and an increase in albumin in the urine of transgenic mice is seen   (MGI Ref ID J:89252)
  • administration of an angiotensin II receptor antagonist improved this condition   (MGI Ref ID J:89252)
• decreased urine osmolality
  • transgenic mice produce dilute urine but are able to produce concentrated urine following water deprivation   (MGI Ref ID J:89252)
• increased circulating creatinine level
  • serum creatinine is elevated in transgenic mice   (MGI Ref ID J:89252)
• immune system phenotype
• kidney inflammation
  • vascular, glomerular, and tubointerstitial changes indicative of hypertensive nephrosclerosis are seen in transgenic mice   (MGI Ref ID J:89252)
  • cortical sections show inflammatory infiltrates, fibroid necrosis and arterial disruption   (MGI Ref ID J:89252)
  • administration of an angiotensin II receptor antagonist ameliorated these pathological changes   (MGI Ref ID J:89252)
• renal/urinary system phenotype
• albuminuria
  • urine protein/creatinine ratios are elevated and an increase in albumin in the urine of transgenic mice is seen   (MGI Ref ID J:89252)
  • administration of an angiotensin II receptor antagonist improved this condition   (MGI Ref ID J:89252)
• decreased urine osmolality
  • transgenic mice produce dilute urine but are able to produce concentrated urine following water deprivation   (MGI Ref ID J:89252)
• kidney inflammation
  • vascular, glomerular, and tubointerstitial changes indicative of hypertensive nephrosclerosis are seen in transgenic mice   (MGI Ref ID J:89252)
  • cortical sections show inflammatory infiltrates, fibroid necrosis and arterial disruption   (MGI Ref ID J:89252)
  • administration of an angiotensin II receptor antagonist ameliorated these pathological changes   (MGI Ref ID J:89252)
• polyuria   (MGI Ref ID J:89252)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cardiovascular Research
Heart Abnormalities
Hypertension
Other

Endocrine Deficiency Research
Kidney Defects

Internal/Organ Research
Kidney Defects

Metabolism Research
Enzyme Deficiency

Research Tools
Cardiovascular Research
Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(Alb1-Ren)2Unc
Allele Name		transgene insertion 2, University of North Carolina
Allele Type		Transgenic (random, expressed)
Common Name(s)		RenTgMK; Tg(Alb1-Ren)1Smi;
Mutation Made By		Dr. Oliver Smithies,   University of North Carolina
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC1/TC-1
ES Cell Line Strain		129S6/SvEvTac
Expressed Gene		Ren1, renin 1 structural, mouse, laboratory
Promoter		Alb1, Albumin , Mouse
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. [MGI Ref ID J:89252]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Alb1-Ren)1Unc, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Caron KM; James LR; Kim HS; Knowles J; Uhlir R; Mao L; Hagaman JR; Cascio W; Rockman H; Smithies O. 2004. Cardiac hypertrophy and sudden death in mice with a genetically clamped renin transgene. Proc Natl Acad Sci U S A 101(9):3106-11. [PubMed: 14978280]  [MGI Ref ID J:88650]

Caron KM; James LR; Kim HS; Morham SG; Sequeira Lopez ML; Gomez RA; Reudelhuber TL; Smithies O. 2002. A genetically clamped renin transgene for the induction of hypertension. Proc Natl Acad Sci U S A 99(12):8248-52. [PubMed: 12034874]  [MGI Ref ID J:89252]

Additional References

Tg(Alb1-Ren)2Unc related

Barrick CJ; Lenhart PM; Dackor RT; Nagle E; Caron KM. 2012. Loss of receptor activity-modifying protein 3 exacerbates cardiac hypertrophy and transition to heart failure in a sex-dependent manner. J Mol Cell Cardiol 52(1):165-74. [PubMed: 22100352]  [MGI Ref ID J:183659]

Caron K; Hagaman J; Nishikimi T; Kim HS; Smithies O. 2007. Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males. Proc Natl Acad Sci U S A 104(9):3420-5. [PubMed: 17360661]  [MGI Ref ID J:125933]

Caron KM; James LR; Lee G; Kim HS; Smithies O. 2005. Lifelong genetic minipumps. Physiol Genomics 20(2):203-9. [PubMed: 15585607]  [MGI Ref ID J:95789]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, hemizygous (heterozygous) mice can be bred with wildtype littermates.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Noncarrier
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

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.

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