2022 Fiscal Year Final Research Report
Generation of mouse models of renal cancer malignant transformation targeting Hippo pathway and therapeutic application
| Project/Area Number |
18K07070
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Oita University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Keywords | Hippoパスウェイ / ノックアウトマウス / 腎癌 |
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| Outline of Final Research Achievements |
In this study, with the aim of creating a model that mimics the development and malignant transformation of renal cancer, I generated mice in which the Hippo pathway component SAV1 and the tumor suppressor gene VHL gene were knocked out in the kidney.
SAV1 homo-knockout mouse died soon after birth with reduced kidney weight and renal dysfunction. Histologically, these mice showed renal cyst formation with atypia, accompanied by activation of YAP. These renal cysts were histologically distinct from those in VHL homo-knockout mice. SAV1 and VHL double homo-knockout mice also died shortly after birth. Although none of these mice developed renal cancer, a mouse model for the development of atypical renal cysts was generated by inactivation of the Hippo pathway.
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| Free Research Field |
実験病理学
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| Academic Significance and Societal Importance of the Research Achievements |
腎癌の発症と悪性化を模倣するモデルを作製し、新たな治療法の開発を目指した。腎発生異常をきたしたため、癌の発症には至らなかったが、新たに腎臓の正常発生にSAV1が関わっていることを証明できた。また異型を伴う腎嚢胞を形成するモデルマウスの作成ができたことから、異型を伴う腎嚢胞が持つ病態を解析する礎となる研究としての意義を持つと考える。
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