Format

Send to

Choose Destination
PLoS One. 2016 Nov 18;11(11):e0166974. doi: 10.1371/journal.pone.0166974. eCollection 2016.

Long-Range Control of Renin Gene Expression in Tsukuba Hypertensive Mice.

Author information

1
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
2
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
3
Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki, Japan.

Abstract

Renin, a rate-limiting enzyme in the renin-angiotensin system, is regulated to maintain blood pressure homeostasis: renin gene expression in the kidney is suppressed in a hypertensive environment. We found that expression of a 15-kb human RENIN (hREN) transgene was aberrantly upregulated (>4.2-fold), while the endogenous mouse renin (mRen) gene was suppressed (>1.7-fold) in Tsukuba hypertensive mice (THM), a model for genetically induced hypertension. We then generated transgenic mice using a 13-kb mRen gene fragment that was homologous to the 15-kb hREN transgene and found that its expression was also upregulated (>3.1-fold) in THM, suggesting that putative silencing elements of the renin genes were distally located in the loci. We next examined the possible role of a previously identified mouse distal enhancer (mdE) located outside of the 13-kb mRen gene fragment. Deletion of the mdE in the context of a 156-kb mRen transgene did not affect its transcriptional repression in THM, implying that although the silencing element of the mRen gene is located within the 156-kb fragment tested, it is distinct from the mdE. Consistent with these results, deletion of the 63-kb region upstream of the mdE from the endogenous mRen gene locus abrogated its transcriptional repression in THM. We finally tested whether dysregulation of the short renin transgenes also occurred in the fetal or neonatal kidneys of THM and found that their expression was not aberrantly upregulated, demonstrating that aberrant regulation of short renin transgenes commences sometime between neonate and adult periods.

PMID:
27861631
PMCID:
PMC5115840
DOI:
10.1371/journal.pone.0166974
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center