Investigation of gene mutation specific to canine bone marrow diseases

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05967
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: The University of Tokyo
• Principal Investigator: Goto-Koshino Yuko (後藤裕子) 東京大学, 大学院農学生命科学研究科(農学部), 特任准教授 (80436518)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 真性多血症 / 犬 / 網羅的解析

Outline of Final Research Achievements

Investigation of a polycythemia vera (PV)-specific gene mutation was performed using two dogs diagnosed as PV. CD3 positive lymphocytes were purified as normal cell population, and the remaining CD3 negative nucleated cells were separated as population containing abnormal clone. Two populations were compared to find abnormal clone-specific gene mutation.　Whole exome sequencing was designed at first, however, because of the low quality of genome DNA purified from CD3 positive normal cell population, target resequencing of the cancer related genes was adopted instead. Multiple gene mutations specific to the population containing abnormal clone were extracted, however, none of the mutation was validated by Sanger sequencing. It would be necessary to enrich the abnormal clone, for example, purification of erythroid progenitors from PV dogs, for further analysis.

Free Research Field

獣医内科学

Academic Significance and Societal Importance of the Research Achievements

真性多血症は血液幹細胞の異常によって異常な赤血球増多が起こる疾患である。異常な血液幹細胞は赤血球だけでなく白血球にも分化することが知られているが、白血病と異なり、細胞の機能は正常である。
本研究は犬における真性多血症の原因遺伝子を探索し、人の真性多血症において高頻度に認められるJAK2遺伝子変異と同様に診断マーカーとして確立すること、さらに治療のターゲットとしての可能性を検討することを目的として行ったが、研究期間内には有望な遺伝子変異を見出すことができなかった。今後は異常細胞のみを単離して解析を試みる予定である。