2023 Fiscal Year Final Research Report
Analysis of the onset site and pathological progression process of ulcerative colitis in model mice with luminescence reporter gene
| Project/Area Number |
21K07917
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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 53010:Gastroenterology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Irie Atsushi 熊本大学, 大学院生命科学研究部(医), 講師 (30250343)
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| Co-Investigator(Kenkyū-buntansha) |
竹田 直樹 熊本大学, 生命資源研究・支援センター, 助教 (90304998)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 潰瘍性大腸炎 / 炎症性腸疾患 / 小胞体ストレス / HLA-DR / トランスジェニックマウス / 動物モデル |
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| Outline of Final Research Achievements |
The HLA-DR4tgm homozygotes established by the applicants presented with dwarfism, diarrhea, and rectal prolapse, and most of them die within six months of birth. Histopathological analysis revealed numerous mononuclear cell infiltrates in the colon and ulcerative colitis-like findings, including disruption of epithelial cell shape and markedly reduced mucus production, which were not seen in the colons of normal heterozygotes. The presence of endoplasmic reticulum stress due to high expression of HLA-DR4 and Helicobacter japonicus are essential for the development of this colitis. Using a luminescent reporter gene (ERAI-Akaluc) to detect endoplasmic reticulum stress, colitis-affected areas were observed over time in the same individual mice. The affected area was shown to begin near the rectal antrum and migrate ascending.
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| Free Research Field |
免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
潰瘍性大腸炎（ulcerative colitis、以下 UC）は原因不明の難病であり、その根本治療法の確立が切望されている。UCの発症に関わる因子として、腸内細菌叢と免疫系の異常が疑われているが、起因菌や免疫系の異常を誘導する機構は未だよくわかっていない。申請者らが樹立したHLA-DR4tgmホモ接合体は、起因菌の経口投与により人為的にUCを発症させることができ、従来のUCモデルマウスよりもより自然なUCの病態が得られる。このマウスを用いることにより、大腸炎病態の進展過程を明らかにし、UC発症メカニズムの理解とその予防法・治療法開発の端緒を得ることを目指す。
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