PUBLICATION

Aromatic L-Amino Acid Decarboxylase (AADC) Is Crucial for Brain Development and Motor Functions

Authors
Shih, D.F., Hsiao, C.D., Min, M.Y., Lai, W.S., Yang, C.W., Lee, W.T., and Lee, S.J.
ID
ZDB-PUB-130903-34
Date
2013
Source
PLoS One   8(8): e71741 (Journal)
Registered Authors
Hsiao, Chung-Der, Lee, Shyh-Jye
Keywords
Larvae, Zebrafish, Embryos, Swimming, Neurons, Dopamine, Apoptosis, Serotonin
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Aromatic-L-Amino-Acid Decarboxylases/genetics
  • Aromatic-L-Amino-Acid Decarboxylases/physiology*
  • Brain/embryology*
  • Embryo, Nonmammalian
  • Embryonic Development/genetics*
  • Molecular Sequence Data
  • Motor Activity/genetics*
  • Sequence Homology, Amino Acid
  • Zebrafish*/embryology
  • Zebrafish*/genetics
PubMed
23940784 Full text @ PLoS One
Abstract

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.

Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping