Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development

TYROSINE hydroxylase catalyses the initial, rate-limiting step in the catecholamine biosynthetic pathway. Catecholamines, which include dopamine, noradrenaline, and adrenaline, are important neurotransmitters and hormones that regulate visceral functions, motor coordination and arousal in adults 1 . The gene encoding tyro-sine hydroxylase becomes transcriptionally active in developing neuroblasts during mid-gestation of rodent embryos, before the onset of neurotransmission 2–6 . Here we show that inactivation of both tyrosine hydroxylase alleles results in mid-gestational lethality: about 90% of mutant embryos die between embryonic days 11.5 and 15.5, apparently of cardiovascular failure. Administration of L-DOPA (dihydroxyphenylalanine), the product of the tyrosine hydroxylase reaction, to pregnant females results in complete rescue of mutant mice in utero . Without further treatment, however, they die before weaning. We conclude that catecholamines are essential for mouse fetal development and postnatal survival