| 研究概要 |
Runx1 protein is a transcription factor which has critical functions in development. Deletion of Runx1 in mouse not only exhibit defected developmental processes, but also various autoimmune diseases, especially a human asthma-like pathology. Our laboratory showed that this pathology is caused by overexpression of IL-4, a cytokine essential for asthma pathogenesis, in the absence of Runx1. This observation prompted us to propose that Runx1 might actively function to control immune responses in addition to the well-established roles in development.
In search of molecular mechanisms by which Runx1 regulates immune responses, we discovered a novel lncRNA (long non-coding RNA) around Runx1 gene locus and found that this lncRNA (Runx1-lncRNA1) is expressed in helper T lymphocytes and specifically bind to Runx1 protein. Interestingly, siRNA (small interfering RNA)-mediated knockdown of Runx1-lncRNA1 from helper T lymphocytes in vitro resulted in phenotypes resembling deletion of Runx1 such as increases in IL-4 expression. Therefore, we hypothesize that Runx1-lncRNA1 might be necessary for fine-tuning of Runx1 function.
To further elucidate the function of Runx1-lncRNA1 in a more physiological setting, we generated a genetically modified mouse line in which this lncRNA is permanently deleted. Our preliminary data show that helper T lymphocytes of this knockout mouse indeed overexpress IL-4 marginally but significantly. At age of 4-5 months, this knockout mouse seems to show evidences of spontaneous infiltration of leukocytes into airway which is observed in Runx1-deficient mouse.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Some of the experiments planned for H25 is not finished yet, but the most important objective of research for H26, the generation of Runx1-lncRNA1 knockout mouse, is already finished.
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