Pathophysiologic role of histamine: evidence clarified by histidine decarboxylase gene knockout mice.

The role of histamine in various murine disease models has been clarified using histidine decarboxylase gene knockout mice. The mice were generated using conventional gene-targeting methods. Studies, including ours, using knockout mice have shown that the activity of histamine is not limited to allergic, peptic and neurologic functions as in the old paradigm, but extends to other processes related to wound healing, circulatory disease, immunology, oncology and infectious disease. The recent observation of the activity of newly cloned histamine receptors and a pathophysiologic effect of histamine has dramatically expanded our understanding of the scope of histamine function.