Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions.
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 i...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3734303?pdf=render |
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| author | De-Fen Shih Chung-Der Hsiao Ming-Yuan Min Wen-Sung Lai Chianne-Wen Yang Wang-Tso Lee Shyh-Jye Lee |
| author_facet | De-Fen Shih Chung-Der Hsiao Ming-Yuan Min Wen-Sung Lai Chianne-Wen Yang Wang-Tso Lee Shyh-Jye Lee |
| author_sort | De-Fen Shih |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T19:42:56Z |
| format | Article |
| id | doaj.art-643df191a4f443e48c6951b37a6ff260 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T19:42:56Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-643df191a4f443e48c6951b37a6ff2602022-12-22T00:52:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7174110.1371/journal.pone.0071741Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions.De-Fen ShihChung-Der HsiaoMing-Yuan MinWen-Sung LaiChianne-Wen YangWang-Tso LeeShyh-Jye LeeAromatic 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.http://europepmc.org/articles/PMC3734303?pdf=render |
| spellingShingle | De-Fen Shih Chung-Der Hsiao Ming-Yuan Min Wen-Sung Lai Chianne-Wen Yang Wang-Tso Lee Shyh-Jye Lee Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions. PLoS ONE |
| title | Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions. |
| title_full | Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions. |
| title_fullStr | Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions. |
| title_full_unstemmed | Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions. |
| title_short | Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions. |
| title_sort | aromatic l amino acid decarboxylase aadc is crucial for brain development and motor functions |
| url | http://europepmc.org/articles/PMC3734303?pdf=render |
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