Cdx1 induced intestinal metaplasia in the transgenic mouse stomach: comparative study with Cdx2 transgenic mice
Cdx1 induced intestinal metaplasia in the transgenic mouse stomach: comparative study with Cdx2 transgenic mice
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DOI：
10.1136/gut.2003.032482
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发表时间：
2004-10-01
期刊：
影响因子：
24.5
通讯作者：
Sugano, K
中科院分区：
文献类型：
--
作者：
Mutoh, H;Sakurai, S;Sugano, K
背景与目的：胃肠化生主要由幽门螺杆菌感染引起，被认为是胃腺癌的癌前病变。肠化生粘膜在人胃粘膜中表达肠特异性同源框基因 Cdx1 和 Cdx2。我们等人报道了胃上皮异位表达Cdx2在转基因小鼠模型中产生肠化生。方法：为了阐明Cdx1和Cdx2在肠化生中作用的差异，我们制备了胃粘膜表达Cdx1的转基因小鼠，并比较Cdx1诱导的胃粘膜形态变化和Cdx2诱导的肠化生。结果：Cdx1转基因小鼠的胃粘膜完全被替换。肠化生粘膜，由所有四种肠上皮细胞类型组成：吸收性肠上皮细胞、杯状细胞、肠内分泌细胞和潘氏细胞。潘氏细胞位于肠化生粘膜的上部，在 Cdx2 转基因小鼠中未被识别。在 Cdx2 转基因小鼠中诱导的假幽门腺化生在 Cdx1 转基因小鼠中未被识别。 Cdx1诱导的肠化生粘膜中增殖细胞核抗原（PCNA）阳性细胞呈弥漫性散在分布，而Cdx2诱导的肠化生粘膜中PCNA阳性细胞位于化生粘膜基底部。 Cdx1转基因小鼠胃部的肠化生粘膜明显厚于野生型或Cdx2转基因小鼠胃部。结论：我们证实Cdx1诱导胃肠化生，但其在分化、结构和增殖方面与Cdx2诱导的肠化生不同。
Background and aims: Gastric intestinal metaplasia, which is mainly induced by Helicobacter pylori infection, is thought to be a precancerous lesion of gastric adenocarcinoma. Intestinal metaplastic mucosa expresses intestine specific homeobox genes, Cdx1 and Cdx2, in the human gastric mucosa. We and others have reported that ectopic expression of Cdx2 in the gastric epithelium generates intestinal metaplasia in the transgenic mouse model.Methods: To clarify the differences in the roles of Cdx1 and Cdx2 in intestinal metaplasia, we generated transgenic mice expressing Cdx1 in the gastric mucosa and compared Cdx1 induced gastric mucosal morphological changes with Cdx2 induced intestinal metaplasia.Results: The gastric mucosa in Cdx1 transgenic mice was completely replaced by intestinal metaplastic mucosa, consisting of all four intestinal epithelial cell types: absorptive enterocytes, goblet, enteroendocrine, and Paneth cells. Paneth cells, which were not recognised in Cdx2 transgenic mice, were in the upper portion of the intestinal metaplastic mucosa. Pseudopyloric gland metaplasia, which was induced in Cdx2 transgenic mice, was not recognised in Cdx1 transgenic mice. Proliferating cell nuclear antigen ( PCNA) positive cells were diffusely scattered in Cdx1 induced intestinal metaplastic mucosa while PCNA positive cells in Cdx2 induced intestinal metaplastic mucosa were in the base of the metaplastic mucosa. Intestinal metaplastic mucosa of Cdx1 transgenic mouse stomach was significantly thicker than that of wildtype or Cdx2 transgenic mouse stomach.Conclusions: We have confirmed that Cdx1 induced gastric intestinal metaplasia but that it differed from Cdx2 induced intestinal metaplasia in differentiation, structure, and proliferation.