Description

Strain Information

Type Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Thomas 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 Alb

007238	B6.Cg-Tg(Alb-PLG)1Dgi/J
002226	C57BL/6J-Tg(Alb1HBV)44Bri/J

View Strains carrying other alleles of Alb     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tg(Alb1-Ren)1Unc/?

        129S6/SvEvTac-Tg(Alb1-Ren)1Unc

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

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

Tg(Alb1-Ren)1Unc/0

        involves: 129S6/SvEvTac * C57BL/6

• life span-post-weaning/aging
• premature death (MGI Ref ID J:88650)
  • about 60% of transgenic males die suddenly between 6 and 8 months of age
• behavior/neurological phenotype
• polydipsia (MGI Ref ID J:89252)
  • transgenic mice drink significantly more than non-transgenic mice
• cardiovascular system phenotype
• cardiac hypertrophy (MGI Ref ID J:88650)
  • 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
• decreased heart rate (MGI Ref ID J:88650)
  • in mice that die prematurely a prolonged and progressive bradycardia is seen
  • transgenics show a significant decrease in heart rate variability compared to wild-type mice
• hypertension (MGI Ref ID J:89252)
  • transgenic mice have blood pressures more than 25 mmHg higher than wild-type mice
  • administration of an angiotensin II receptor antagonist lowered blood pressure in transgenic mice down to that seen in wild-type mice
  • transgenic mice have blood pressures more than 25 mmHg higher than wild-type mice
• homeostasis/metabolism phenotype
• albuminuria (MGI Ref ID J:89252)
  • urine protein/creatinine ratios are elevated and an increase in albumin in the urine of transgenic mice is seen
  • administration of an angiotensin II receptor antagonist improved this condition
• decreased urine osmolality (MGI Ref ID J:89252)
  • transgenic mice produce dilute urine but are able to produce concentrated urine following water deprivation
• increased circulating creatinine level (MGI Ref ID J:89252)
  • serum creatinine is elevated in transgenic mice
• immune system phenotype
• kidney inflammation (MGI Ref ID J:89252)
  • vascular, glomerular, and tubointerstitial changes indicative of hypertensive nephrosclerosis are seen in transgenic mice
  • cortical sections show inflammatory infiltrates, fibroid necrosis and arterial disruption
  • administration of an angiotensin II receptor antagonist ameliorated these pathological changes
• renal/urinary system phenotype
• albuminuria (MGI Ref ID J:89252)
  • urine protein/creatinine ratios are elevated and an increase in albumin in the urine of transgenic mice is seen
  • administration of an angiotensin II receptor antagonist improved this condition
• decreased urine osmolality (MGI Ref ID J:89252)
  • transgenic mice produce dilute urine but are able to produce concentrated urine following water deprivation
• kidney inflammation (MGI Ref ID J:89252)
  • vascular, glomerular, and tubointerstitial changes indicative of hypertensive nephrosclerosis are seen in transgenic mice
  • cortical sections show inflammatory infiltrates, fibroid necrosis and arterial disruption
  • administration of an angiotensin II receptor antagonist ameliorated these pathological changes
• 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

Allele Symbol		Tg(Alb1-Ren)1Unc
Allele Name		transgene insertion 1, University of North Carolina
Allele Type		Targeted (other)
Common Name(s)		RenTg; RenTgMK; Tg(Alb1-Ren)1Smi;
Mutation Made By		Oliver Smithies,   University of North Carolina
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC-1
ES Cell Line Strain		129S6/SvEvTac
Expressed Gene		Ren1, renin 1 structural, mouse, laboratory
Promoter		Alb, albumin, mouse, laboratory
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, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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)1Unc related

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]

Pandya K; Kim HS; Smithies O. 2006. Fibrosis, not cell size, delineates beta-myosin heavy chain reexpression during cardiac hypertrophy and normal aging in vivo. Proc Natl Acad Sci U S A 103(45):16864-9. [PubMed: 17068123]  [MGI Ref ID J:132484]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

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

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development and On Hold

Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Noncarrier
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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