A genetic model for development, physiology and behavior of zebrafish larvae devoid of catecholamines

Dopamine and noradrenaline have conserved roles in control of physiology and behaviors of vertebrates. However, vertebrate genetic systems completely devoid of catecholamines are not available. We have generated a genetic zebrafish model completely devoid of catecholamines by combining mutations in all three genes involved in L-DOPA synthesis: the tyrosine hydroxylase genes th and th2, and tyrosinase tyr. We found catecholamine-deficient zebrafish larvae to be viable and to develop an anatomically normal nervous system including catecholaminergic neuron somata and projections, albeit with reduced cell numbers detected in some clusters. 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 how physiology and neural circuit function are regulated in catecholamine deficient larvae.