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Identification of histamine producing cells by the gene-rescue method

基因拯救法鉴定组胺产生细胞

基本信息

批准号：
15390076
负责人：
OHTSU Hiroshi
金额：
$ 9.15万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390076/
关键词：
Histamine Knockout mice L-histidine decarboxylase Wound healing Transgenic mice Bronchial asthma Central nervous system Gastric juice secrestion トランスジェニックマウス

项目摘要

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).

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中。组胺是由组氨酸在 L-组氨酸脱羧酶的催化下合成的。我们制备了组氨酸脱羧酶基因缺陷的小鼠（HDC-/-），以阻止组胺的产生，并将其用于评估多种疾病模型中组胺的活性。1.支气管哮喘模型的研究我们通过使用卵清蛋白和明矾作为过敏原，在HDC+/+和HDC-/-小鼠中制作了支气管哮喘模型。这两只基因分型小鼠的支气管过敏性没有太大差异，但与 HDC+/+ 小鼠相比，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产生了在鸡肌动蛋白启动子序列控制下引入HDCcDNA的转基因小鼠。这些小鼠表现出与加速相关的伤口愈合过程，这与 HDC-/- 小鼠中观察到的表型完全相反。我们证明bFGF是传导组胺作用的物质之一。（提交）3.组胺对中枢神经系统和胃液分泌的影响。我们阐明组胺对于昼夜节律、行为和惊厥很重要（Mol Brain Res，Euro J Neurosci，Epilepsia 2004）。 HDC-/-小鼠表现出胃壁肥厚（Am J Physiol 2003）。组胺对于暴发性肝炎的恢复很重要（Gastroenterol 2004）。组胺对于动脉粥样硬化中内皮细胞的生成和斑块形成也是非常重要的物质（Circ Res 2005）。