Identification of histamine producing cells by the gene-rescue method

组胺是其在体内发挥生物活性的重要物质之一。它们已知的著名活性表现在过敏状态、宿主防御反应、胃液分泌和神经传递。组胺是在L组氨酸脱羧酶的催化下由组氨酸合成的。为了阻止组胺的产生，我们建立了组氨酸脱羧酶基因缺陷的小鼠(HDC-/-)，并将其用于评估几种疾病模型中组胺的活性。1.哮喘模型的研究我们用卵蛋白和明胶作为过敏原，建立了HDC+/+和HDC-/-小鼠的哮喘模型。HDC-/-小鼠与HDC+/+小鼠相比，支气管超敏反应差异不大，但HDC-/-小鼠的嗜酸性粒细胞浸润受到强烈抑制。(Am J Respir Crit Care Med 2003)2.转基因小鼠的产生我们在鸡肌动蛋白启动子序列的控制下，获得了高密度脂蛋白基因的转基因小鼠。这些小鼠表现出加速伤口愈合的过程，这与HDC-/-小鼠的表现完全相反。我们证明bFGF是组胺作用的转导物质之一。(提交)3.组胺在中枢神经系统和胃液分泌中的作用。我们阐明了组胺对昼夜节律、行为和惊厥的重要作用(Mol Brain Res，Euro J Neurosci，Epilepsia 2004)。HDC-/-小鼠显示胃壁肥大(Am J Physiol 2003)。组胺对于暴发性肝炎的康复很重要(胃肠病，2004年)。组胺也是动脉粥样硬化中内皮细胞生成和斑块形成的非常重要的物质(Circ Res 2005)。

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).