Development of histamine H2 receptor-deficient mouse model by gene targeting.

为了分析组胺H2受体不仅在胃肠道，而且在包括神经和血液系统在内的全身生理调节中的功能作用，我们试图建立一个组胺H2受体缺失的小鼠模型。作为第一步，我们克隆了小鼠组胺H2受体基因，包括未翻译的5‘区。利用这个基因，我们构建了一个靶向载体，并将其引入ES细胞。筛选出整合了基因打靶片段的ES细胞后，将这些细胞导入囊胚。几只处于嵌合状态的小鼠出生了，但到目前为止还没有证实生殖系传播。因此，我们已经制备了几个整合了靶向载体的ES克隆，并将其注射到囊胚中，以获得具有种系传递的重组基因的小鼠。

To analyze the functional role of histamine H2 receptors on the physiological regulations not only in gastrointestinal tract but also in whole body including neurological and hematological systems, we tried to develop a mouse model that lacks histamine H2 receptor. As a first step, we cloned mouse histamine H2 receptor gene including non-translated 5' region. With this gene, we constructed a targeting vector that is introduced in ES cells. After selection of ES cells that showed integration of gene targeting segment, these cells are introduced in blastcysts. Several mice in chimeric state were born, but so far no germline transmission was confirmed. Thus, several other ES clones with integration of targeting vectors have been prepared and injected in blastcysts in order to obtain a mouse with germline transmission of the recombinant gene.