1. ¹Department of Gastroenterology and Hepatology, School of Medicine (Formerly Second Department of Internal Medicine and Anatomy, Shimane Medical University), Shimane University, Izumo, Japan
2. ²Department of Anatomy, School of Medicine (Formerly Second Department of Internal Medicine and Anatomy, Shimane Medical University), Shimane University, Izumo, Japan
3. ³Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan
4. ⁴Department of Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories), Tohoku University Graduate School of Medicine, Sendai, Japan

Correspondence: Dr Y Kadowaki, Department of Gastroenterology and Hepatology, School of Medicine (Formerly Second Department of Internal Medicine, Shimane Medical University), Shimane University, 89-1, Enya-cho, Izumo, Shimane 693-8501, Japan. E-mail: y-kado@momo.so-net.ne.jp

Received 26 October 2005; Revised 3 April 2006; Accepted 3 April 2006; Published online 14 August 2006.

Abstract

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.