Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare pediatric 
neuro-metabolic disease in children. Due to the lack of an animal model, its 
pathogenetic mechanism is poorly understood. To study the role of AADC in brain 
development, a zebrafish model of AADC deficiency was generated. We identified 
an aadc gene homolog, dopa decarboxylase (ddc), in the zebrafish genome. 
Whole-mount in situ hybridization analysis showed that the ddc gene is expressed 
in the epiphysis, locus caeruleus, diencephalic catecholaminergic clusters, and 
raphe nuclei of 36-h post-fertilization (hpf) zebrafish embryos. Inhibition of 
Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) 
reduced brain volume and body length. We observed increased brain cell apoptosis 
and loss of dipencephalic catecholaminergic cluster neurons in ddc morphants 
(ddc MO-injected embryos). Seizure-like activity was also detected in ddc 
morphants in a dose-dependent manner. ddc morphants had less sensitive touch 
response and impaired swimming activity that could be rescued by injection of 
ddc plasmids. In addition, eye movement was also significantly impaired in ddc 
morphants. Collectively, loss of Ddc appears to result in similar phenotypes as 
that of ADCC deficiency, thus zebrafish could be a good model for investigating 
pathogenetic mechanisms of AADC deficiency in children.