Creation of abnormal muscle development model of zebrafish and novel drug platform

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08674
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyushu University
• Principal Investigator: KONDO Takuya 九州大学, 医学研究院, 助教 (00644725)
• Co-Investigator(Kenkyū-buntansha): 永田 公二 九州大学, 大学病院, 講師 (20419568) ; 桐野 浩輔 九州大学, 大学病院, その他 (00621707)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ヒルシュスプルング病類縁疾患 / ゼブラフィッシュ / LMOD1

Outline of Final Research Achievements

We decided to use intestinal dysfunction as a smooth muscle aplasia model, and induced deletion of the LMOD1 gene in fertilized zebrafish eggs using CRISPR/Cas9. Regarding intestinal peristalsis in young fish, we used Spatiotemporal Mapping, which analyzes reduced excretion and intestinal peristalsis using videos, to obtain findings on intestinal peristalsis.
qPCR revealed that in addition to decreased expression of lmod1a, expression of other smooth muscle components ACTA2 and MYH11, as well as MYOD1, which is involved in smooth muscle development, was also decreased, indicating a decrease in the components of smooth muscle itself. It was confirmed. In addition, in order to track the behavior of Pax7, we have created a model in which the GFP gene is inserted, and are attempting to track the behavior of Pax7-expressing cells as they grow.

Free Research Field

小児外科

Academic Significance and Societal Importance of the Research Achievements

本研究では、主に筋肉の発生に関連する疾患の原因解明と、その治療法模索のために計画しました。筋肉には横紋筋と平滑筋があり、今回は平滑筋の発生や機能解明を重視しました。特に、消化管平滑筋の異常により生じると考えられている疾患で、現在有効な治療法のないヒルシュスプルング病類縁疾患を主なターゲットとし、その原因遺伝子とされている遺伝子を対象として用い、その発病機序を解明するとともに、疾患の新たな治療法や創薬に役立つ可能性のある研究となっています。