Genetic ablation of parietal cells in transgenic mice: A new model for analyzing cell lineage relationships in the gastric mucosa
Genetic ablation of parietal cells in transgenic mice: A new model for analyzing cell lineage relationships in the gastric mucosa
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DOI：
10.1073/pnas.93.6.2431
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发表时间：
1996-03-19
影响因子：
11.1
通讯作者：
Levenson, R
中科院分区：
文献类型：
--
作者：
Canfield, V;West, AB;Levenson, R
哺乳动物胃的胃粘膜含有几种专门用于分泌酸、消化酶、粘液和激素的分化细胞类型。了解这些细胞谱系是否均源自共同的干细胞一直是一个具有挑战性的问题。我们使用遗传方法分析小鼠胃内祖细胞的个体发育，将单纯疱疹病毒1胸苷激酶靶向转基因小鼠胃粘膜内的壁细胞，并通过用抗疱疹药物更昔洛韦治疗动物来消除壁细胞。更昔洛韦治疗导致壁细胞完全消融、胃腺溶解以及主细胞和粘液产生细胞的损失。药物治疗的终止导致所有主要胃上皮细胞类型的重新出现和腺体结构的恢复。我们的结果表明胃粘膜存在多能干细胞。壁细胞消融应该提供一个模型来分析胃内细胞谱系关系以及胃损伤和修复的机制。
The gastric mucosa of mammalian stomach contains several differentiated cell types specialized for the secretion of acid, digestive enzymes, mucus, and hormones. Understanding whether each of these cell lineages is derived from a common stem cell has been a challenging problem. We have used a genetic approach to analyze the ontogeny of progenitor cells within mouse stomach, Herpes simplex virus 1 thymidine kinase was targeted to parietal cells within the gastric mucosa of transgenic mice, and parietal cells were ablated by treatment of animals with the antiherpetic drug ganciclovir. Ganciclovir treatment produced complete ablation of parietal cells, dissolution of gastric glands, and loss of chief and mucus-producing cells, Termination of drug treatment led to the reemergence of all major gastric epithelial cell types and restoration of glandular architecture. Our results imply the existence of a pluripotent stem cell for the gastric mucosa. Parietal cell ablation should provide a model for analyzing cell lineage relationships within the stomach as well as mechanisms underlying gastric injury and repair.