Skip to main content

In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer.

Publication ,  Journal Article
Yamada, T; Horiuchi, M; Morishita, R; Zhang, L; Pratt, RE; Dzau, VJ
Published in: J Clin Invest
September 1995

DBA/2J mouse contains two renin gene loci (Ren1d and Ren2d). Ren2d but not Ren1d is expressed in submandibular gland (SMG) while both are expressed in the kidney. Based on vitro studies, we have postulated that a negative regulatory element (NRE) in the renin gene promoter is involved in its tissue-specific expression. In this study, we examined the molecular mechanism at the in vivo level using direct gene transfer. Fragments of the Ren1d or Ren2d promoter were fused to a chloramphenicol acetyltransferase (CAT) gene expression vector. These constructs complexed in fusogenic liposomes were injected directly into the mouse SMG or intraarterially into the mouse kidney via the renal artery. The vector containing the CAT exhibited readily detectable in vivo expressions in both SMG and kidney. In the SMG, Ren1d fragment containing the NRE abolished CAT expression while deletion of the NRE restored CAT expression. The homologous fragment from the Ren2d promoter did not inhibit CAT expression while deletion of the 150-bp insertion resulted in the inhibition. Cotransfection of Ren1d construct with Ren1d-NRE oligonucleotides as transcriptional factor decoy restored CAT expression. Contrary to the SMG, transfection with Ren1d fragment-CAT construct or Ren2d fragment-CAT construct into the kidney resulted in similar levels of CAT expression. Interestingly, human c-myc NRE oligonucleotides which share homology with Ren1d-NRE competed effectively with these oligonucleotides for the regulation of Ren1d gene expression in vivo. This NRE sequence is also homologous to silencer elements found in multiple mammalian genes, suggesting the presence of a family of NRE/NRE binding proteins regulating expression of diverse genes.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

September 1995

Volume

96

Issue

3

Start / End Page

1230 / 1237

Location

United States

Related Subject Headings

  • Transfection
  • Renin
  • Regulatory Sequences, Nucleic Acid
  • Receptors, Antigen, T-Cell
  • Promoter Regions, Genetic
  • Organ Specificity
  • Molecular Sequence Data
  • Mice, Inbred DBA
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yamada, T., Horiuchi, M., Morishita, R., Zhang, L., Pratt, R. E., & Dzau, V. J. (1995). In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer. J Clin Invest, 96(3), 1230–1237. https://doi.org/10.1172/JCI118156
Yamada, T., M. Horiuchi, R. Morishita, L. Zhang, R. E. Pratt, and V. J. Dzau. “In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer.J Clin Invest 96, no. 3 (September 1995): 1230–37. https://doi.org/10.1172/JCI118156.
Yamada T, Horiuchi M, Morishita R, Zhang L, Pratt RE, Dzau VJ. In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer. J Clin Invest. 1995 Sep;96(3):1230–7.
Yamada, T., et al. “In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer.J Clin Invest, vol. 96, no. 3, Sept. 1995, pp. 1230–37. Pubmed, doi:10.1172/JCI118156.
Yamada T, Horiuchi M, Morishita R, Zhang L, Pratt RE, Dzau VJ. In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer. J Clin Invest. 1995 Sep;96(3):1230–1237.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

September 1995

Volume

96

Issue

3

Start / End Page

1230 / 1237

Location

United States

Related Subject Headings

  • Transfection
  • Renin
  • Regulatory Sequences, Nucleic Acid
  • Receptors, Antigen, T-Cell
  • Promoter Regions, Genetic
  • Organ Specificity
  • Molecular Sequence Data
  • Mice, Inbred DBA
  • Mice
  • Male