A genetic model for development, physiology and behavior of catecholamine-deficient zebrafish larvae.

Dopamine and noradrenaline have conserved roles in control of physiology and behaviors of vertebrates. However, vertebrate genetic models completely devoid of catecholamines are not available. We generated genetically catecholamine-free zebrafish larvae by combining mutations in all three genes involved in L-DOPA biosynthesis: the tyrosine hydroxylase genes th and th2, and tyrosinase tyr. Here we show that catecholamine-deficient 5 day-old zebrafish larvae are viable and develop an anatomically normal nervous system, including the full complement of catecholaminergic neuron somata and projections. In contrast, selected physiological functions that depend on catecholamines are impaired, including hatching and heart rate regulation upon temperature challenges. Spontaneous locomotion and optomotor behaviors are also impaired. Despite the changes observed, it is surprising that larvae develop a largely normal behavioral repertoire. Our model will be useful to investigate the activities of additional neurotransmitters expressed in catecholaminergic neurons, and how physiology and neural circuit function are regulated in the absence of catecholamines.