Identification of histamine producing cells by the gene-rescue method

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Histamine is one of the important substances for their biological activites in the body. Their known famous activities are shown in allergic state, host defense reactions, gastric juice secretion, and nervous transmission. Histamine is synthesized from histidine catalyzed with L-histidine decarboxylase. We generated the mice (HDC-/-) which have the defect in histidine decarboxylase gene in order to stop the production of histamine and used it for the assessment of the activity of histamine in several disease models.1.A study for a bronchial asthma modelWe produced a bronchial asthma model in HDC+/+ and HDC-/-mice by using Ovalbumin and alum for their allergen. The bronchial hypersensitivity was not so different between these two genotyped mice but eosinophilic infiltration was strongly supressed in HDC-/-mice compared to HDC+/+ mice. (Am J Respir Crit Care Med 2003)2.Generation of the transgenic miceWe generated the transgenic mice which was introduced HDCcDNA under the control of chicken actin promoter sequence. These mice showed an accerelated wound healing process which was the completely opposite phenotype to seen in HDC-/-mice. We proved that bFGF is one of the substances transducting the effect of histamine. (submitting)3.The effect of histamine in CNS and in secretion of gastric juice.We clarified that histamine is important for the circadian rhythm, behavior, and convulsion (Mol Brain Res, Euro J Neurosci, Epilepsia 2004). HDC-/-mice showed hypertrophic gastric wall (Am J Physiol 2003). Histamine was important for the recovery from fulminant hepatitis (Gastroenterol 2004). Histamine was also very important substance for the generation of endothelial cells and plaque formation in atherosclerosis (Circ Res 2005).