Development of Helicobacter pylori infection model in BALB/c mice with domestic cagA-positive and -negative strains in Taiwan

We aimed to develop an H. pylori-infected mouse model using clinically stor ed strains in Taiwan and to test whether development of H. pylori infection in an in vivo animal model is related to the status of the cagA gene. A to tal of 100 male BALB/c mice, 6-8 weeks old, including 80 in the experimenta l group and 20 in the control group, were used. Two clinically stored H. py lori isolates, a cagA-positive and a cagA-negative strain, were selected to induce the H. pylori infection in half (N = 40) of the mice in the experim ental group. Bacterial isolates of 0.8 x 10(9) CFU/ml were orally inoculate d in each mouse of the experimental group for three consecutive days. Ten m ice in the control group were sacrificed to confirm the initial absence of H. pylori. Eight weeks after inoculation of the experimental group and no i noculation of the remaining 10 mice of the control group, each mouse was ki lled. Gastrectomy was then performed for rapid urease test (CLOtest) and hi stology. In the control group, none of 20 mice had positive results from th e CLOtest or histology. In contrast, excluding eight of 80 mice that died b efore the eighth week, 90.3% (65/72) of the mice challenged with H. pylori showed persistent presence of H. pylori by histology. The severity of gastr itis at the eighth week was more evident in H. pylori-infected mice than in control and noninfected mice (P < 0.05). Although gastritis was more sever e in mice inoculated with the cagA-positive strain than with the cagA-negat ive strain, the rates of H. pylori infection in mice were not different bet ween cagA-positive and -negative strains (91.4% vs 89.2%, P > 0.05). In sum mary, stored strains of H. pylori can be applied to induce an infection mod el in BALB/c mice. The less virulent cagA-negative strain can induce H. pyl ori infection in mice as effectively as the cagA-positive strain. The high prevalence of cagA-positive strains in Taiwanese patients may be related to factors other than only the cagA gene of the bacteria.