Reg I-knockout mice reveal its role in regulation of cell growth that is required in generation and maintenance of the villous structure of small intestine
Reg I-knockout mice reveal its role in regulation of cell growth that is required in generation and maintenance of the villous structure of small intestine
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DOI：
10.1038/sj.onc.1209799
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发表时间：
2007-01-01
期刊：
影响因子：
8
通讯作者：
Kinoshita, Y.
中科院分区：
文献类型：
--
作者：
Ose, T.;Kadowaki, Y.;Kinoshita, Y.
Reg I（再生基因产物I）是一种生长因子，在胃粘膜结构的生成和再生中起核心作用。另一方面，在胃肠道组织中，小鼠的Reg I mRNA在小肠中表达水平最高。在本研究中，为了明确Reg I蛋白在小肠中的作用，我们检测了Reg I表达的时空格局以及Reg I敲除小鼠在组织中的表型。在野生型小鼠中，免疫组织化学定位了位于肠绒毛下半部分的吸收细胞中Reg I蛋白的表达。直到胚胎第13天（E13），胎儿肠仍缺乏绒毛结构时，才检测到Reg I的表达；但在E17时，随着胎儿肠绒毛的形成和成熟，其含量显著增加。在成年Reg i基因敲除小鼠的小肠中，光镜下观察到吸收细胞排列不密集，呈圆形异常形态，电镜检查显示这些细胞与基膜的连接明显松散。抗增殖细胞核抗原染色和抗ki67染色显示，敲除小鼠小肠黏膜的增殖细胞数量明显减少。5-溴脱氧尿苷单针标记的细胞迁移速度在敲除小鼠中明显变慢。根据上述Reg I表达的时间模式，这些Reg I敲除小鼠的表型从E17开始出现。regi被认为是产生和维持小肠绒毛结构所需的细胞生长调节剂。
Reg I (regenerating gene product I) is a growth factor that plays a central role in the generation and regeneration of the gastric mucosal architecture. On the other hand, mouse Reg I mRNA is expressed at the highest levels in the small intestine among the gastrointestinal tissues. In the current study, with the aim to clarify the role of Reg I protein in the small intestine, the temporal and spatial pattern of Reg I expression and the phenotype of Reg I-knockout mice in the tissue were examined. In the wild-type mice, immunohistochemistry localized Reg I protein expression in absorptive cells located in the lower half of the intestinal villi. Reg I expression was undetectable until embryonic day 13 (E13), when the fetal intestine still lacks villous structure; however, it dramatically increased at E17 along with the formation and maturation of the fetal intestinal villi. In the small intestine of the adult Reg I-knockout mice, less densely packed, round-shaped aberrant morphology of the absorptive cells was observed light microscopically, and electron microscopical examination revealed a strikingly loose connection of these cells to the basement membrane. Antiproliferating cell nuclear antigen staining and anti-Ki67 staining demonstrated the marked decrease in the number of proliferating cells in the small intestinal mucosa of the knockout mice. The cell migration speed visualized by one shot labeling of 5-bromodeoxyuridine was significantly slower in the knockout mice. These phenotypes of Reg I-knockout mice emerged, in accordance with the temporal pattern of Reg I expression described above, from E17. Reg I was considered to be a regulator of cell growth that is required to generate and maintain the villous structure of the small intestine.