Sequence analysis, chromosomal location, and developmental expression of the mouse preproendothelin-1 gene.

Recent studies have designated endothelins (ETs) as morphogenetic factors in embryonic development. In the present study, we cloned and characterized the mouse preproendothelin-1 (preproET-1) gene (Edn1) and examined its expression in reference to development. Edn1 comprises five exons, and the open reading frame encodes the 202-amino-acid preproET-1. The sequences and structural organization of Edn1 are highly homologous to those of other species, especially in the terminal 200-bp sequence of the 3'-noncoding region. Interspecific backcross mapping located Edn1 in the central region of chromosomal 13, where a mouse mutation, congenital hydrocephalus (ch), is also mapped. The highest expression of Edn1 mRNA is detected in the lung in adult mice, whereas Edn1 is predominantly expressed in the epithelium and mesenchyme of the pharyngeal arches and in the endothelium of the large arteries. Edn1 expression and ET-1 peptide levels in the lung progressively increased during the perinatal stage, whereas the expression of Edn3, a gene encoding ET-3, reciprocally decreases. These results suggest that Edn1 expression is developmentally regulated in different tissues and organs in mice in a spatial- and temporal-specific manner.