Development, characterization, and utilization of an intestinal xenograft model for infectious disease research

Paired xenografts of near-term fetal rabbit jejunum were subcutaneously implanted in the backs of athymic nude (nu/nu) mice. At 3 to 4 weeks post-implantation, the grafts had histologic, ultrastructural, and biochemical (lactase, sucrase, alkaline phosphatase, leucine aminopeptidase) parameters comparable to age-matched control rabbits. Four weeks post-transplantation the xenografts were intraluminally inoculated with various strains of lapine attaching and effacing E. coli or group A rotavirus. Infection with 2 strains of E. coli resulted in typical light microscopic and ultrastructural lesions of attachment and effacement. Immunohistochemical analysis of rotavirus-infected xenografts demonstrated rotavirus antigen within enterocytes. These lesions are comparable to those in conventional rabbits. Intestinal xenografts are a novel, highly controlled, and reproducible model which may have unique applications in the study of enteric diseases. The model provides anatomically and biochemically correct intestinal mucosal epithelium uncomplicated by variables such as enteric flora, host immune response, gastric, hepatic, and pancreatic secretions and is susceptible to infection by specific enteropathogens. Xenografts, therefore, may be a viable alternative in certain investigations where whole animals, ligated intestinal loops, organ cultures, or cell cultures might otherwise be chosen.