STRUCTURE, EXPRESSION, AND GENOMIC MAPPING OF THE MOUSE NATRIURETIC PEPTIDE TYPE-B GENE

The structure of the mouse natriuretic peptide type-B (BNP) gene was determined by isolating and sequencing genomic clones. The mouse BNP gene was structurally similar to other natriuretic peptide genes and comprised three exons and two introns. Expression of the mouse BNP gene was found only in cardiac tissue as determined by ribonuclease protection analyses. Initiation of transcription was 31 bp downstream from a consensus TATA box as determined by primer extension analysis of cardiac RNA. Comparative DNA sequence analysis identified several DNA elements with potential transcriptional regulatory function. Comparative amino acid sequence analysis showed that the N-terminal portion of the mouse and rat BNP precursors was more conserved than the C-terminal 45-amino-acid sequence that constitute the bioactive BNP-45 peptide. The proteolytic processing site (RXXR-S) generating bioactive BNPs was highly conserved among all BNP precursors and was identical to the consensus site of furin, a calcium-dependent serine endoprotease. Finally, the BNP gene was mapped using recombinant inbred DNA and a polymerase chain reaction-based restriction fragment-length polymorphism assay to mouse chromosome 4 near the atrial natriuretic factor (Anf) locus. No recombination event between Bnp and Anf was evident in the 39 recombinant inbred and inbred strains examined. This physical linkage between the two natriuretic peptide genes expressed in cardiac tissue may be important for their transcriptional regulation.