Study on ketone body metabolism and its defects: mainly gene expression mechanism of SCOT gene

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591505
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Gifu University
• Principal Investigator: FUKAO Toshiyuki 岐阜大学, 医学(系)研究科(研究院), 教授 (70260578)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ケトン体代謝 / 先天代謝異常症 / スプライシング / 遺伝子異常 / 遺伝子発現調節 / OXCT1 / ChiPアッセイ

Outline of Final Research Achievements

I mainly analyzed the mechanism of liver-specific suppression of SCOT gene.
1)Liver specific suppression activity was not observed in human and mouse 3’non-coding region sequences when examined by a luciferase assay. 2)Using ChiP assay with RNA polymerase 2 antibody, transcriptional activity of SCOT hene regions were compared with that of GAPDH in mouse heart, kidney and liver tissues. SCOT transcription in the liver was much low comparing to that in the kidney and heart. These data suggest that SCOT gene expression is suppressed mainly at the transcriptional level in liver. I also confirmed that a missense mutation c.949G>A(D317N) caused exon 10 skipping in the mini-gene splicing experiment, indicating that this mutation functions as a splicing mutation rather than amissense mutation.

Free Research Field

小児科学