Pathophysiology of non-regenerative anemia in miniature dachshunds

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K15991
• 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: Hokkaido University
• Principal Investigator: Morishita Keitaro 北海道大学, 獣医学研究院, 助教 (30637046)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 非再生性貧血 / ミニチュア・ダックスフンド / 脾臓 / 補体

Outline of Final Research Achievements

Miniature dachshunds are known to be predisposed to non-regenerative anemia.Based on the finding that splenectomy dramatically restores hematopoiesis, we performed a multi-omics analysis using the spleen and serum samples from afected dogs.We identified a total of 1,385 diffeerntially expression genes between spleen samples from normal dogs and affected dogs. Of these, 707 genes were upregulated, including S100A12, S100A8, and S100A9.Immunohistochemistry confirmed significantly higher expression of S100A8/A9 in the spleen of affected dogs.A total of 22 proteins were differentially expressed between the pre- and post-splenectomy serum samples. The reactome pathways “Lectin pathway of complement activation” were over-represented in our list of pathways upregulated before splenectomy.

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

本研究の結果から、罹患犬脾臓におけるS100A8/A9蛋白質の発現増加が補体レクチン経路を活性化し、赤芽球系細胞のオプソニン化によって非再生性貧血を発症するという新たな仮説が導かれた。本疾患の病態を分子レベルで検証した報告は限られており、研究成果は補体関連疾患という既知の理解とは異なる疾患概念の可能性を示した。市場には補体関連疾患に対する種々の補体標的薬が販売されていることから、本研究の成果が病態解明の足掛かりとなり、補体標的薬による新たな治療戦略の開発につながり得る。