Untraditional methods for targeting the kidney in transgenic mice

Bianco, Robert A.; Keen, Henry L.; Lavoie, Julie L.

doi:10.1152/ajprenal.00207.2003

Cited by 10 publications

(12 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the consequences of ovarian expression of constitutively active AT1AR remains undefined, its expression in the brain could have obvious consequences for the regulation of arterial pressure. Remarkably, the chimeric KAP promoter (termed KAP2) originally developed by us (5) has been used by us and others to target PPAR␣ (28), AGT (37), and renin (23) without notable expression in the brain. AT1 receptors in the brain have long been known to be an important regulator of arterial pressure, hydromineral balance, vasopressin release, and sympathetic drive, and therefore a contribution of brain AT1AR in the KAP2-AT1AR-N111G model cannot be excluded.…”

Section: Discussionmentioning

confidence: 99%

“…To generate the KAP2-AT1AR-N111G transgenic mice, a cDNA fragment encoding rat AT1AR (N111G) was inserted into the Not I site of the KAP2 construct. The KAP2 construct is composed of 1,542 bp of KAP promoter fused to a gutted coding region of the hAGT gene and has been shown to drive PCT-specific gene expression in an androgeninducible manner (5). The rat AT1AR (N111G) cDNA fragment was amplified from the vector pRc-CMV-AT1R (provided by Dr. Walter G. Thomas, Baker Medical Research Institute, Melbourne, Australia) (1).…”

Section: Generation Of Kap2-at1ar-n111g and Kap2-at1ar-ko Micementioning

confidence: 99%

See 1 more Smart Citation

Renal proximal tubule angiotensin AT1A receptors regulate blood pressure

Weatherford

Davis

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

View full text Add to dashboard Cite

All components of the renin angiotensin system necessary for ANG II generation and action have been reported to be present in renal proximal convoluted tubules. Given the close relationship between renal sodium handling and blood pressure regulation, we hypothesized that modulating the action of ANG II specifically in the renal proximal tubules would alter the chronic level of blood pressure. To test this, we used a proximal tubule-specific, androgen-dependent, promoter construct (KAP2) to generate mice with either overexpression of a constitutively active angiotensin type 1A receptor transgene or depletion of endogenous angiotensin type 1A receptors. Androgen administration to female transgenic mice caused a robust induction of the transgene in the kidney and increased baseline blood pressure. In the receptor-depleted mice, androgen administration to females resulted in a Cre recombinase-mediated deletion of angiotensin type 1A receptors in the proximal tubule and reduced blood pressure. In contrast to the changes observed at baseline, there was no difference in the blood pressure response to a pressor dose of ANG II in either experimental model. These data, from two separate mouse models, provide evidence that ANG II signaling via the type 1A receptor in the renal proximal tubule is a regulator of systemic blood pressure under baseline conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Generation Of Kap2-at1ar-n111g and Kap2-at1ar-ko Micementioning

confidence: 99%

Renal proximal tubule angiotensin AT1A receptors regulate blood pressure

Weatherford

Davis

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, powerful new techniques to analyze gene function in a nephron-specific manner are now being used (reviewed in Refs. 3,15,33). The first requisite to generate these cell-or tissue-specific knockouts is to characterize the promoter of a particular gene to determine whether this region contains all the necessary elements that confer expression in a cell-specific manner.…”

Section: Discussionmentioning

confidence: 99%

UT-A urea transporter promoter, UT-Aα, targets principal cells of the renal inner medullary collecting duct

Fenton¹,

Shodeinde²,

Knepper³

2006

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

The urea transporters, UT-A1 and UT-A3, two members of the UT-A gene family, are localized to the terminal portion of the inner medullary collecting duct (IMCD). In this manuscript, we demonstrate that 4.2 kb of the 5'-flanking region of the UT-A gene (UT-Aalpha promoter) is sufficient to drive the IMCD-specific expression of a heterologous reporter gene, beta-galactosidase (beta-Gal), in transgenic mice. RT-PCR, immunoblotting, and immunohistochemistry demonstrate that within the kidney, transgene expression is confined to the terminal portion of the IMCD. Colocalization studies with aquaporin-2 show that expression is localized to the principal cells of the IMCD2 and IMCD3 regions. Utilizing beta-Gal activity assays, we further show that within the kidney, the beta-Gal transgene can be regulated by both water restriction and glucocorticoids, similar to the regulation of the endogenous UT-A gene. These results demonstrate that 4.2 kb of the UT-Aalpha promoter is sufficient to drive expression of a heterologous reporter gene in a tissue-specific and cell-specific fashion in transgenic mice.

show abstract

“…Finally, it is worth mentioning that the design of the KAP2-hREN transgene construct, which is inserting hREN in place of the coding region of hAGT while retaining downstream (noncoding) exons, was the product of studies suggesting that a transcriptional enhancer in exon 5 and the 3Ј-untranslated region of the hAGT gene cooperated with the KAP promoter to drive proximal tubule and androgen-dependent expression (1). Constructs containing only the KAP promoter segment fused to reporter genes such as ␤-Gal and luciferase failed to drive proximal tubule-specific expression (Sigmund CD, unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

Increased blood pressure in transgenic mice expressing both human renin and angiotensinogen in the renal proximal tubule

Lavoie

Lake-Bruse

2004

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

The purpose of this study was to evaluate the physiological significance of a tissue renin-angiotensin system in the proximal tubule of the kidney. To accomplish this, we produced mice that express human renin (hREN) under the control of the kidney androgen-regulated promoter (KAP), which is androgen responsive. One of the lines expressed the hREN transgene primarily in the kidney. Renal expression of the transgene was undetectable in females but could be induced by testosterone treatment. Because the renin-angiotensin system is species specific, we bred KAP2-hREN mice with the mice expressing human angiotensinogen under the same promoter (KAP-hAGT) to produce offspring that expressed both transgenes. We measured mean arterial blood pressure (MAP) in the carotid artery of double-transgenic and control mice using radiotelemetry. Double-transgenic female mice had a normal baseline MAP (116 +/- 4 mmHg, n = 8), which increased by 15 mmHg after 2 wk of testosterone treatment, and returned to baseline after elimination of the testosterone pellet. The change in arterial pressure paralleled the change in plasma testosterone. There was no MAP change in testosterone-treated control littermates. We conclude that dual production of renin and angiotensinogen in the renal proximal tubule can result in a systemic increase in arterial pressure. These data support a role for a tissue-specific renin-angiotensin system in the renal proximal tubule that contributes to the regulation of systemic blood pressure.

show abstract

Untraditional methods for targeting the kidney in transgenic mice

Cited by 10 publications

References 38 publications

Renal proximal tubule angiotensin AT1A receptors regulate blood pressure

Renal proximal tubule angiotensin AT1A receptors regulate blood pressure

UT-A urea transporter promoter, UT-Aα, targets principal cells of the renal inner medullary collecting duct

Increased blood pressure in transgenic mice expressing both human renin and angiotensinogen in the renal proximal tubule

Contact Info

Product

Resources

About