Mechanism analysis of progressive neurological abnormalities in xeroderma pigmentosum group A patients

2016 Fiscal Year Final Research Report

• Project/Area Number: 26550042
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Nara Medical University
• Principal Investigator: Mori Toshio 奈良県立医科大学, 医学部, 研究教授 (10115280)
• Research Collaborator: Brooks P. J. ; Nakane Hironobu ; Hayashi Masaharu
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 色素性乾皮症 / 神経障害 / 酸化的DNA損傷 / サイクロプリン / モノクローナル抗体 / DNA修復異常

Outline of Final Research Achievements

Xeroderma pigmentosum group A (XP-A) patients develop progressive neurological abnormalities, which has been hypothesized to be associated with a type of oxidatively generated DNA damage called purine 8,5’-cyclo-2’-deoxynucleosides. Thus, we generated a monoclonal antibody specific for 8,5’-cyclo-2’-deoxynadenosine (Cyclo-dA) in DNA. The immunoassay revealed a linear dose-response between known amounts of Cyclo-dA in oligonucleotides and the antibody binding to them with a detection sensitivity of about 1 lesion/10<6> bases in a 1 ug DNA sample. We compared the amounts of Cyclo-dA accumulated in organs between wild type and XP-A mice with ages from 5 months to 29 months. We found that XP-A mice accumulate significantly higher amounts of Cyclo-dA in brains than do wild type mice, supporting the hypothesis.

Free Research Field

遺伝情報制御学