Molecular cloning of the complementary DNA and gene that encode mouse brain natriuretic peptide and generation of transgenic mice that overexpress the brain natriuretic peptide gene

Yoshihiro Ogawa, Hiroshi Itoh, Naohisa Tamura, Shin Ichi Suga, Takaaki Yoshimasa, Masahiro Uehira, Saburo Matsuda, Shozo Shiono, Hirofumi Nishimoto, Kazuwa Nakao

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

Brain natriuretic peptide (BNP) is a cardiac hormone that occurs predominantly in the ventricle. To study the roles of BNP in chronic cardiovascular regulation, we isolated mouse BNP cDNA and genomic clones, and generated transgenic mice with elevated plasma BNP concentration. The mouse BNP gene was organized into three exons and two introns. Two BNP mRNA species were identified, which were generated by the alternative mRNA splicing. The ventricle was a major site of BNP production in mice. Mouse preproBNP was a 121- (or 120-) residue peptide, and its COOH-terminal 45-residue peptide was the major storage form in the heart. Transgenic mice carrying the human serum amyloid P component/mouse BNP fusion gene were generated so that the hormone expression is targeted to the liver. In the liver of these mice, considerable levels of BNP mRNA and peptide were detected, reaching up to 10-fold greater than in the ventricle. These animals showed 10- to 100-fold increase in plasma BNP concentration accompanied by elevated plasma cyclic GMP concentration, and had significantly lower blood pressure than their nontransgenic littermates. The present study demonstrates that these mice provide a useful model system with which to assess the roles of BNP in cardiovascular regulation and suggests the potential usefulness of BNP as a long-term therapeutic agent.

Original languageEnglish
Pages (from-to)1911-1921
Number of pages11
JournalJournal of Clinical Investigation
Volume93
Issue number5
DOIs
Publication statusPublished - 1994 May
Externally publishedYes

Keywords

  • atrial natriuretic peptide
  • blood pressure
  • cardiovascular regulation
  • cyclic guanosine monophosphate
  • serum amyloid P component

ASJC Scopus subject areas

  • Medicine(all)

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