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Type Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N7 Donating Investigator Curt Sigmund, University of Iowa Description
This strain carries a human angiotensinogen transgene whose expression results in angiotensinogen plasma concentrations 150X that normally found in human plasma. These mice are normotensive but become transiently hypertensive when injected with a bolus of purified renin. A chronically hypertensive mouse can by created by breeding this strain with a strain carrying the human renin transgene (C57BL/6-TgN(hREN)9Sig; 002750). The mean arterial pressure of the double transgenic is ~155 mmHg (controls ~111 mmHg). Both systolic and diastolic blood pressures are elevated.Development
A human genomic clone that included all five exons and intervening intron sequences was injected into B6SJLF2 eggs. The founder number for this strain is 204.1. In the nomenclature it is recorded as 2041 as punctuation marks are not allowed.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(hAGT)2041Sig/0
involves: C57BL/6 * SJL/JView Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Cardiovascular Research
Hypertension
| Allele Symbol | Tg(hAGT)2041Sig | ||
|---|---|---|---|
| Allele Name | transgene insertion 2041, Curt Sigmund | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | A+; Hu-AGT-TG; hAng; | ||
| Mutation Made By | Curt Sigmund, University of Iowa | ||
| Strain of Origin | (C57BL/6 x SJL/J)F2 | ||
| Expressed Gene | AGT, angiotensinogen (serpin peptidase inhibitor, clade A, member 8), human | ||
| Molecular Note | The 14 kb transgenic construct contained the entire human angiotensinogen gene (approximately 11.5 kb) and 5' (1.2 kb) and 3' (1.4 kb) flanking sequence. Sequence analysis showed that the construct contained the M235T variant but not the T174M variant. The human AGT promoter drove high levels of expression in the liver and kidney. Expression was also detected in the heart, adrenal gland, and adipose tissue, and at very low levels in the brain and submandibular gland. Sexually dimorphic expression, in which expression was higher in males, was observed in the kidney and adrenal gland. Lines 204.1 (2041) and 204.3 (2043) were created and transgenic mice on a C57BL/6 background show angiotensinogen plasma concentrations 150X that normally found in human plasma. [MGI Ref ID J:79944] | ||
Genotyping Protocols
Tg(hAGT)2041Sig, STD PCR, vers. 2
Helpful Links
Optimizing PCR Protocols
Yang G; Merrill DC; Thompson MW; Robillard JE; Sigmund CD. 1994. Functional expression of the human angiotensinogen gene in transgenic mice. J Biol Chem 269(51):32497-502. [PubMed: 7798251] [MGI Ref ID J:79944]
Davisson RL; Yang G; Beltz TG; Cassell MD; Johnson AK; Sigmund CD. 1998. The brain renin-angiotensin system contributes to the hypertension in mice containing both the human renin and human angiotensinogen transgenes. Circ Res 83(10):1047-58. [PubMed: 9815152] [MGI Ref ID J:79945]
Merrill DC; Thompson MW; Carney CL; Granwehr BP; Schlager G; Robillard JE; Sigmund CD. 1996. Chronic hypertension and altered baroreflex responses in transgenic mice containing the human renin and human angiotensinogen genes. J Clin Invest 97(4):1047-55. [PubMed: 8613528] [MGI Ref ID J:79859]
Sinn PL; Davis DR; Sigmund CD. 1999. Highly regulated cell type-restricted expression of human renin in mice containing 140- or 160-kilobase pair P1 phage artificial chromosome transgenes. J Biol Chem 274(50):35785-93. [PubMed: 10585461] [MGI Ref ID J:58897]
Yang G; Sigmund CD. 1998. Developmental expression of human angiotensinogen in transgenic mice. Am J Physiol 274(5 Pt 2):F932-9. [PubMed: 9612331] [MGI Ref ID J:47720]
Tg(hAGT)2041Sig relatedBaumbach GL; Sigmund CD; Faraci FM. 2003. Cerebral arteriolar structure in mice overexpressing human renin and angiotensinogen. Hypertension 41(1):50-5. [PubMed: 12511529] [MGI Ref ID J:128819]
Brand M; Lamande N; Sigmund CD; Larger E; Corvol P; Gasc JM. 2006. Angiotensinogen modulates renal vasculature growth. Hypertension 47(6):1067-74. [PubMed: 16636191] [MGI Ref ID J:128231]
Cvetkovic B; Keen HL; Zhang X; Davis D; Yang B; Sigmund CD. 2002. Physiological significance of two common haplotypes of human angiotensinogen using gene targeting in the mouse. Physiol Genomics 11(3):253-62. [PubMed: 12388794] [MGI Ref ID J:81310]
Davisson RL; Ding Y; Stec DE; Catterall JF; Sigmund CD. 1999. Novel mechanism of hypertension revealed by cell-specific targeting of human angiotensinogen in transgenic mice. Physiol Genomics 1(1):3-9. [PubMed: 11015555] [MGI Ref ID J:135870]
Davisson RL; Kim HS; Krege JH; Lager DJ; Smithies O; Sigmund CD. 1997. Complementation of reduced survival, hypotension, and renal abnormalities in angiotensinogen-deficient mice by the human renin and human angiotensinogen genes. J Clin Invest 99(6):1258-64. [PubMed: 9077534] [MGI Ref ID J:39934]
Davisson RL; Yang G; Beltz TG; Cassell MD; Johnson AK; Sigmund CD. 1998. The brain renin-angiotensin system contributes to the hypertension in mice containing both the human renin and human angiotensinogen transgenes. Circ Res 83(10):1047-58. [PubMed: 9815152] [MGI Ref ID J:79945]
Didion SP; Ryan MJ; Baumbach GL; Sigmund CD; Faraci FM. 2002. Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen. Am J Physiol Heart Circ Physiol 283(4):H1569-76. [PubMed: 12234811] [MGI Ref ID J:79459]
Didion SP; Sigmund CD; Faraci FM. 2000. Impaired endothelial function in transgenic mice expressing both human renin and human angiotensinogen. Stroke 31(3):760-4; discussion 765. [PubMed: 10700516] [MGI Ref ID J:61307]
Ding Y; Stec DE; Sigmund CD. 2001. Genetic evidence that lethality in angiotensinogen-deficient mice is due to loss of systemic but not renal angiotensinogen. J Biol Chem 276(10):7431-6. [PubMed: 11096065] [MGI Ref ID J:135051]
Iida S; Baumbach GL; Lavoie JL; Faraci FM; Sigmund CD; Heistad DD. 2005. Spontaneous stroke in a genetic model of hypertension in mice. Stroke 36(6):1253-8. [PubMed: 15914769] [MGI Ref ID J:130409]
Merrill DC; Thompson MW; Carney CL; Granwehr BP; Schlager G; Robillard JE; Sigmund CD. 1996. Chronic hypertension and altered baroreflex responses in transgenic mice containing the human renin and human angiotensinogen genes. J Clin Invest 97(4):1047-55. [PubMed: 8613528] [MGI Ref ID J:79859]
Morimoto S; Cassell MD; Sigmund CD. 2002. The brain renin-angiotensin system in transgenic mice carrying a highly regulated human renin transgene. Circ Res 90(1):80-6. [PubMed: 11786522] [MGI Ref ID J:131098]
Sakai K; Agassandian K; Morimoto S; Sinnayah P; Cassell MD; Davisson RL; Sigmund CD. 2007. Local production of angiotensin II in the subfornical organ causes elevated drinking. J Clin Invest 117(4):1088-95. [PubMed: 17404622] [MGI Ref ID J:121252]
Sethi S; Iida S; Sigmund CD; Heistad DD. 2006. Renal thrombotic microangiopathy in a genetic model of hypertension in mice. Exp Biol Med (Maywood) 231(2):196-203. [PubMed: 16446496] [MGI Ref ID J:129130]
Sinn PL; Davis DR; Sigmund CD. 1999. Highly regulated cell type-restricted expression of human renin in mice containing 140- or 160-kilobase pair P1 phage artificial chromosome transgenes. J Biol Chem 274(50):35785-93. [PubMed: 10585461] [MGI Ref ID J:58897]
Yang G; Sigmund CD. 1998. Developmental expression of human angiotensinogen in transgenic mice. Am J Physiol 274(5 Pt 2):F932-9. [PubMed: 9612331] [MGI Ref ID J:47720]
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 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.
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 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.
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| 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. | ||
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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