Abstract | OBJECTIVE: To construct the folic acid deficient model in zebrafish and observe the abnormal cardiac phenotypes, to find the optimal period for supplementing folic acid that can most effectively prevent the heart malformation induced by folic acid deficiency, and to investigate the possible mechanisms by which folic acid deficiency induces malformations of heart. METHOD: The folic acid deficient zebrafish model was constructed by using both the folic acid antagonist methotrexate (MTX) and knocking-down dhfr ( dihydrofolate reductase gene). Exogenous tetrahydrofolic acid rescue experiment was performed. Folic acid was given to folic acid deficient groups in different periods. The percent of cardiac malformation, the cardiac phenotypes, the heart rate and the ventricular shortening fraction (VSF) were recorded. The out flow tract (OFT) was observed by using fluorescein micro-angiography. Whole-mount in situ hybridization and real-time PCR were performed to detect vmhc, amhc, tbx5 and nppa expressions. RESULT: About (78.00 ± 3.74)% embryos in MTX treated group and (68.00 ± 6.32)% embryos in dhfr knocking-down group had heart malformations, including the abnormal cardiac shapes, the hypogenesis of OFT and the reduced heart rate and VSF. Giving exogenous tetrahydrofolic acid rescued the above abnormalities. Given the folic acid on 8 - 12 hours post-fertilization (hpf), both the MTX treated group (20.20% ± 3.77%) and dhfr knocking-down group (43.40% ± 4.51%) showed the most significantly reduced percent of cardiac malformation and the most obviously improved cardiac development. In folic acid deficient group, the expressions of tbx5 and nppa were reduced while the expressions of vmhc and amhc appeared normal. After being given folic acid to MTX treated group and dhfr knocking-down group, the expressions of tbx5 and nppa were increased. CONCLUSIONS:
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Authors | Shu-na Sun, Yong-hao Gui, Qiu Jiang, Hou-yan Song |
Journal | Zhonghua er ke za zhi = Chinese journal of pediatrics
(Zhonghua Er Ke Za Zhi)
Vol. 48
Issue 12
Pg. 905-12
(Dec 2010)
ISSN: 0578-1310 [Print] China |
PMID | 21215183
(Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- T-Box Domain Proteins
- T-box transcription factor 5
- Atrial Natriuretic Factor
- Folic Acid
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Topics |
- Animals
- Atrial Natriuretic Factor
(metabolism)
- Cell Differentiation
(drug effects)
- Folic Acid
(metabolism)
- Folic Acid Deficiency
(genetics, metabolism)
- Gene Knockdown Techniques
- Heart
(drug effects, embryology, growth & development)
- T-Box Domain Proteins
(metabolism)
- Zebrafish
(embryology, genetics)
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