Abstract：Objective The aim of this study is to develop a mouse model of neural tube defects (NTDs), through interfering a new folate-metabolism-related pathway, i.e., catalyzing the nucleoside triphosphate into the deoxyriboside triphosphate by nucleotide reductase. We further verify the results through comparing our model with previous NTDs mouse models with different metabolic disorders. Methods We fed C57BL/6 mice (7–8 weeks old, 18–20g, Hua Fu Kang Company, Beijing, China) with specific pathogen-free standard mouse chow. Two female mice were mated with one male at 6:00 p.m overnight, and the vaginal plugs were examined at the following morning. The pregnant mice with vaginal plugs were considered as the indicator for 0.5 embryonic day (E 0.5). To find the optimal hydroxyurea (HU) dose, pregnant mice were randomly divided into six groups. On E 7.5, the control group was intraperitoneally injected with 0.9% NaCl. The other five groups were treated with different HU levels. In addition, cell proliferation and apoptosis in the embryonic brain tissues of NTDs mice were measured by western blot assay and immunohistochemistry method.Results NTDs mouse models were established through HU induction. Our results found a decreased amount of PCNA protein and an elevated amount of caspase-3 protein in NTD-embryos, comparing to the control group (P<0.05). The expression level of PCNA was decreased, while Caspase-3 was increased in NTD-embryos, comparing to the control (P<0.05). Our results were consistent with those of previous NTDs model.Conclusion Our study established a NTDs mouse model through inducing the imbalance of cell proliferation and apoptosis after inhibiting nucleotide reductase. We present a new animal model for the further study of neural tube malformations.
官臻, 王秀伟, 朱智强, 岳慧轩, 李莘, 秦佳星, 牛勃, 王建华. 羟基脲诱导神经管畸形小鼠模型及与其他小鼠模型的比较研究[J]. 中国生育健康杂志, 2021, 32(2): 137-142.
GUAN Zhen, WANG Xiuwei, ZHU Zhiqiang, YUE Huixuan, LI Shen, QIN Jiaxing, NIU Bo, WANG Jianhua. The study of neural tube defect mouse model induced byhydroxyurea and comparison with other models. Chinese Journal of Reproductive Health, 2021, 32(2): 137-142.
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