Elevated Blood-Pressure and Craniofacial Abnormalities in Mice Deficient in Endothelin-1

Kurihara Y; Kurihara H; Suzuki H; Kodama T; Maemura K; Nagai R; Oda H; Kuwaki T; Cao WH; Kamada N; Jishage K; Ouchi Y; Azuma S; Toyoda Y; Ishikawa T; Kumada M; Yazaki Y

Nature, Vol.368, No.6473, 703-710, 1994

Kurihara Y, Kurihara H, Suzuki H, Kodama T, Maemura K, Nagai R, Oda H, Kuwaki T, Cao WH, Kamada N, Jishage K, Ouchi Y, Azuma S, Toyoda Y, Ishikawa T, Kumada M, Yazaki Y

The endothelin-l (ET-1) gene was disrupted in mouse embryonic stem cells by homologous recombination to generate mice deficient in ET-1. These : ET-1(-/-) homozygous mice die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs. ET-1(+/-) heterozygous mice, which produce lower levels of ET-1 than wild-type mice, develop elevated blood pressure. These results suggest that ET-1 is essential for normal mouse development and may also play a physiological role in cardiovascular homeostasis.

Keywords:DEVELOPMENTAL DEFECTS;TARGETED DISRUPTION;VENTRAL SURFACE;BINDING-SITES;RAT MEDULLA;GENE;EXPRESSION;PEPTIDE;CELLS;HYPERTENSION