The discovery of new physiological effect of histamine by gene-manipulated mice and its application for the creation of pathological model

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1) We elucidated HDC gene knockout mice. They lack histamine from the whole body ; therefore it is useful for the histamine research.2) We found several interesting phenotypes including behavior, allergic reaction, and inflammation.3) For instance, knockout mice showed no extravasation reaction, confirmed by the Evan's blue leakage from the vessel in the immediate-type skin reaction. Moreover, this disappearance of skin reaction was "rescued" by orally supplemented histamine. This shows that the extravasation reaction succeeded after immediate type allergic reaction is controlled by histamine.4) In the systemic anaphylaxis reaction histamine has been proved to be one of the very important mediators.5) The activity of the mice during the day and night is also controlled with histamine.6) Some response to infection was different between wild type and knockout type.7) It will be high possibility that the mice show different response in tumor infiltration and metastasis. We are planning to irradiate ultraviolet rays or inoculate the cultured cancer cells into the mice and observe the infiltrative and metastatic process.8) We prepared transgenic mice expressing high histamine in the body. We are going to use these mice for the study of histamine effects on the whole body.