Development and characterization of a surgical mouse model of reflux esophagitis and Barrett's esophagus

Abstract

Ideally, an animal model of Barrett's esophagus should recapitulate the human disease histologically and immunohistochemically, and be readily susceptible to genetic manipulation. We have developed such a model using a strain of mice commonly used for transgenic and knockout manipulations. We induced reflux by esophagojejunostomy (EJ) in 20 C57Bl/6 mice. At defined time points, sections of the esophagus were stained with H&E and Alcian blue, and immunohistochemical staining was performed for Sox9 (a transcription factor in Barrett's metaplasia), cytokeratin (CK) 8/18 (a columnar marker) and CK14 (a squamous marker). Procedural mortality was 40% for the first ten animals, 20% for the next 10. Reflux esophagitis developed by 13 weeks, and intestinal metaplasia with goblet cells developed by 34 weeks. The metaplasia expressed CK8/18, but not CK14, and exhibited nuclear immunostaining for Sox9. Nuclear Sox9 was also seen in scattered basal cells of squamous epithelium close to the EJ anastomosis. EJ can be performed successfully in C57Bl/6 mice, resulting in reflux esophagitis and intestinal metaplasia that exhibits phenotypic and molecular features of human Barrett's metaplasia. This surgical model in a mouse strain that is easy to manipulate genetically should be a valuable tool for studying the pathogenesis of Barrett's esophagus.