Investigation on a role of activation-induced cytidine deaminase (AID) for development of enzootic bovine leukosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16008
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: National Agriculture and Food Research Organization
• Principal Investigator: Nishimori Asami 国立研究開発法人農業・食品産業技術総合研究機構, 動物衛生研究部門, 研究員 (80817578)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 牛伝染性リンパ腫 / 腫瘍発症機序 / B細胞 / AID

Outline of Final Research Achievements

Bovine leukemia (BL) is a malignant B-cell lymphoma in cattle caused by the infection of the retrovirus. Although it is known that only 1-5% of the infected cattle develop lymphoma, a mechanism of tumor development in BL cattle is not fully understood. In this study, we focused on activation-induced cytidine deaminase (AID), a host-derived enzyme introducing point mutations to genomic DNA, and examined its relevance with BL onset by analyzing expression levels and functional activities of AID in clinical samples or cell lines. As results, no significant association was observed between them, suggesting that AID was irrelevant to tumor development in BL cattle. Interestingly, an offshoot of our research revealed that point mutations at CpG sites was highly observed within several cancer-related genes in BL cattle.

Free Research Field

獣医学

Academic Significance and Societal Importance of the Research Achievements

これまでヒトの臨床検体や細胞株、およびマウスを用いた実験において、B細胞性リンパ腫とAIDの関連を示唆する報告がなされているが、ウシのリンパ腫との関連性は不明であった。本研究の結果から、BL症例におけるAIDの変異誘導因子としての関連性は低いと推察された。一方で、体細胞変異様式の解析により、BL発症牛では特定の癌関連遺伝子においてCpG部位のC(G)→T(A)変異が高率に起こっていることが明らかになったため、今後より詳細な体細胞変異解析を進めることで、BL発症メカニズムに関して新たな知見が得られると期待できる。