Strain Name:

129S/SvEv-Tg(Alb1-Ren)2Unc/CofJ

Stock Number:

007853

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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).

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.
Specieslaboratory mouse
 
Donating InvestigatorDr. 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-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.

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 ByDr. Oliver Smithies,   University of North Carolina
Strain of Origin129S6/SvEvTac
ES Cell Line NameTC1/TC-1
ES Cell Line Strain129S6/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 & HusbandryWhen maintaining a live colony, hemizygous (heterozygous) mice can be bred with wildtype littermates.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2450.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Embryos

Price (US dollars $)
Frozen Embryo $1600.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3185.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Embryos

Price (US dollars $)
Frozen Embryo $2080.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

General Supply Notes

Control Information

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

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