An in vivo model for gastric physiological and pathophysiological studies in the mouse

Abstract

In vivo models for studying gastrointestinal physiology and pathophysiology are well established in rats. Since a number of genetically modified mice are available there is a need for reliable mouse models. The aim of this project was to develop an in vivo mouse model for gastrointestinal studies. C57bl/6, NMRI and transgenic FVB/N (expressing human alpha-1,3/4-fucosyltransferase) mice were anaesthetized with isoflurane and the gastric mucosa exteriorized for intravital microscopy. Acid-base status and acid secretion were measured and blood pressure was continuously monitored. Gastric mucosal blood flow was recorded by laser-Doppler flowmetry. Mucus thickness and accumulation rate were measured with micropipettes. We have developed an in vivo mouse model for studies of the gastric mucosa. With isoflurane anaesthesia the preparation can be studied for up to 5 h with stable blood pressure and mucosal blood flow. Acid-base status agrees with results from other laboratories. Blood flow increased in both C57bl/6 and alpha1.3/4-FT mice in response to luminal HCl, and the mucus gel could be divided into a firmly and a loosely adherent layer, all comparable with results in the rat. However, the firmly adherent mucus layer was thinner (45 +/- 2 microm), and the mucus accumulation rate lower, than in the rat. Furthermore, both basal and stimulated acid secretion showed lower outputs than in the rat. This model has great potential for investigations of gastrointestinal physiology and pathophysiology and can be applied for Helicobacter pylori infection studies.