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Xiyou Zhou

Mentor: Curt D. Sigmund, Ph.D.
Lab Phone: 335-8926

Functional Analysis of Human Renin Enhancers in vivo

Deletion of Kidney and Chorionic Enhancers of Renin gene.

Renin is a rate-limiting enzyme in the renin-angiotensin system, which regulates blood pressure and electrolyte homeostasis. The RAS system product Ang- II causes vasoconstriction, stimulates aldosterone synthesis, and enhances renal water and salt reabsorption. Renin is tightly regulated, for example, arterial pressure and plasma sodium level regulates renin production. Renin is mainly expressed in kidney Juxtaglomerular (JG) cells, but it is also synthesized in chorionic cells of human placenta and other tissues. Sigmund and other laboratories have demonstrated that the human renin gene has an kidney enhancer, which is 241bp in length and is located 13kb upstream of the transcription start site. The kidney enhancer increases transcription 47-fold in a tumorous cell line from kidney JG cells. Similarly, Pinet and others have found a 224bp enhancer, the so-called chorionic enhancer, located 5.7kb upstream of the renin transcription site which increases transcription 59-fold in chorionic cells, but only about 6-fold in JG cells or lung cells. These two enhancers have not been tested in vivo, and its functions remain unclear. We use a knockout technique developed in the Sigmund laboratory to delete the kidney enhancer and chorionic enhancer upstream the human renin gene located on a BAC in bacterial and then generate transgenic mice to test their physiological functions.

Zhou X, Weatherford ET, Liu X, Born E, Keen HL, Sigmund CD. Dysregulated human renin expression in transgenic mice carrying truncated genomic constructs: evidence supporting the presence of insulators at the renin locus. Am J Physiol Renal Physiol. 2008 Sep;295(3):F642-53. Epub 2008 Jul 16. PubMed PMID: 18632798; PubMed Central PMCID: PMC2536869.

Li H, Zhou X, Davis DR, Xu D, Sigmund CD. An androgen-inducible proximal tubule-specific Cre recombinase transgenic model. Am J Physiol Renal Physiol. 2008 Jun;294(6):F1481-6. Epub 2008 Apr 2. PubMed PMID: 18385272.

Zhou X, Sigmund CD. Chorionic enhancer is dispensable for regulated expression of the human renin gene. Am J Physiol Regul Integr Comp Physiol. 2008 Feb;294(2):R279-87. Epub 2007 Dec 12. PubMed PMID: 18077515; PubMed Central PMCID: PMC2408876.

Zhou X, Davis DR, Sigmund CD. The human renin kidney enhancer is required to maintain base-line renin expression but is dispensable for tissue-specific, cell-specific, and regulated expression. J Biol Chem. 2006 Nov 17;281(46):35296-304. Epub 2006 Sep 21. PubMed PMID: 16990260.

Sherrod M, Davis DR, Zhou X, Cassell MD, Sigmund CD. Glial-specific ablation of angiotensinogen lowers arterial pressure in renin and angiotensinogen transgenic mice. Am J Physiol Regul Integr Comp Physiol. 2005 Dec;289(6):R1763-9. Epub 2005 Aug 18. PubMed PMID: 16109805.