The reason why valproic acid leads to neural tube defct: an analysis using folate-associated gene deficient mice

• Project/Area Number: 25860837
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: KIKUCHI Atsuo 東北大学, 大学病院, 助教 (30447156)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 神経管欠損症 / 葉酸代謝異常 / 小児神経学 / 葉酸代謝 / エピジェネティクス / バルプロ酸

Outline of Final Research Achievements

Neural tube defects are one of the most prevalent congenital anomalies of the central nervous system. We searched the mechanism of pathogenesis of neural tube defects, using Amt knock out mice, defecting glycine cleavage system, which is a component of mitochondrial folate one-carbon metabolism. We obtained Amt+/+ and Amt-/- embryos (E9.5) and DNA was subjected to genome-wide methylome analysis by next generation sequencing. Libraries for next generation sequencing were prepared using post bisulfite adaptor tagging method. We also used bisulfite sequence for CpG methylation analysis of candidate genes.
Although we could perform genome-wide methylome of embryos undergoing neural tube closure, we could not identified any differences in DNA methylation between Amt +/+ and Amt -/-.