دورية أكاديمية
Parental folate deficiency induces birth defects in mice accompanied with increased de novo mutations
| العنوان: | Parental folate deficiency induces birth defects in mice accompanied with increased de novo mutations |
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| المؤلفون: | Ying Zhao, Duoyuan Chen, Jianping Tang, Yufang Zheng, Ji Qi, Hongyan Wang |
| المصدر: | Cell Discovery, Vol 8, Iss 1, Pp 1-13 (2022) |
| بيانات النشر: | Nature Publishing Group, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Cytology |
| مصطلحات موضوعية: | Cytology, QH573-671 |
| الوصف: | Abstract Dietary folate deficiency (FD) is associated with the occurrence of birth defects. However, the mechanisms underlying this association remain elusive. In particular, how FD affects genome stability is unknown. To examine whether a folate-deficient diet can affect genome stability, C57BL/6 mice were maintained on a synthetic diet lacking of folic acid (FA) for two generations. F0 mice received the FD diet beginning at 3 weeks of age, and their offspring (F1) began the FD diet after weaning. Both male and female F1 mice fed the FD diet were intentionally crossed with F1 mice fed the normal diet to produce F2 mice. F2 embryos were dissected and collected at E14.5 and E18.5. The malformation ratio was significantly increased in F2 embryos fed the FD diet for two generations compared to those fed the normal diet. Whole-genome sequencing of multiple sibship with F1 males on the FD diet showed that the de novo mutation (DNM) rate in F2 embryos was three times of the reported spontaneous rate in mice. Furthermore, many DNMs observed in the F2 mice exhibited an allele ratio of 1:3 instead of 2:2, suggesting that these mutations are likely to accumulate in gamete cells as a form of mismatch in the DNA duplex. Our study indicated that FD for two generations significantly enhances DNM accumulation during meiosis, which might contribute to the increased negative birth outcomes among F2 mice. Not only maternal but also paternal FA supplementation is probably also necessary and beneficial to prevent birth defects. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2056-5968 69364303 |
| Relation: | https://doaj.org/toc/2056-5968 |
| DOI: | 10.1038/s41421-021-00364-0 |
| URL الوصول: | https://doaj.org/article/e423ea1d6936430392805efe75de3407 |
| رقم الأكسشن: | edsdoj.423ea1d6936430392805efe75de3407 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20565968 69364303 |
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| DOI: | 10.1038/s41421-021-00364-0 |