2 CARDIAC NATRIURETIC PEPTIDE GENES (ATRIAL-NATRIURETIC-PEPTIDE AND BRAIN NATRIURETIC PEPTIDE) ARE ORGANIZED IN TANDEM IN THE MOUSE AND HUMAN GENOMES

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which act as cardiac hormones, are produced mainly by the atrium and v entricle, respectively, and are involved in body fluid homeostasis and blood pressure control. The ANP and BNP gene expressions ate markedly augmented in ventricles of patients with a wide variety of cardiovasc ular diseases. It has been demonstrated that the ANP and BNP genes are tightly linked on mouse chromosome 4 and on the distal short arm of h uman chromosome 1. However, the precise physical map of the ANP and BN P genes has never been elucidated. In the present study, we characteri zed the genomic DNA fragment containing the ANP and BNP genes in mice and humans. Three genomic DNA clones harboring the entire mouse BNP ge ne were isolated from a 129/Sv mouse genomic DNA library. Nucleotide s equence analysis revealed that a phage clone (lambda mBNP#3) contains at its 3'-end the 5'-flanking region and the first 209-bp sequence of the first exon of the mouse ANP gene. In mice, the BNP gene was locate d about 12 kb upstream of the ANP gene. By polymerase chain reaction, we isolated an approximately 11-kb human genomic DNA fragment containi ng the third exon of the BNP gene and the first and second exons of th e ANP gene. In humans, the BNP gene was located upstream of the ANP ge ne, approximately 8 kb apart. The present study provides the direct ev idence that the ANP and BNP genes are organized in tandem in the mouse and human genomes. (C) 1996 Academic Press Limited