Microbial and histopathologic considerations in the use of mouse models of inflammatory bowel diseases

Abstract

Mouse models provide powerful tools to investigate disease mechanisms and are widely used in inflammatory bowel disease research. However, it is common for reports of mouse model studies to lack potentially important information about the microbial status of the mice and the method used to evaluate disease expression for statistical analysis. For example, it is common practice to state that the mice were housed under specific pathogen-free conditions but provide no further information regarding the presence or absence of organisms such as Helicobacter spp. that are known or likely to affect disease expression, thus omitting information potentially important to the expected phenotype of the mice and their responses to experimental manipulation. We therefore encourage authors to use such terms as "conventional" and "specific pathogen-free" precisely, to state the agents from which the mice are represented to be free, and to provide a brief description of the health monitoring protocol. Descriptions of histopathologic methods used to evaluate colitis in mouse models also often do not include sufficient detail to allow readers to understand and evaluate the methods; in addition, the lesions commonly are shown in photomicrographs that are too small and of too low resolution to be interpreted. Inasmuch as such methods are often the major or only source of data upon which conclusions regarding genotype or experimental treatment effects are based, the method employed should be fully described, and photomicrographs should be of adequate size and resolution to allow independent assessment.

Figure 1

Top, normal colon of C57BL/6 Rag1–/– mouse colonized with Altered Schaedler Flora and Helicobacter hepaticus. Bottom, colitis 3 weeks after transfer of CD45RB(high) T cells into a C57BL/6 Rag1–/– mouse colonized with Altered Schaedler Flora and Helicobacter hepaticus.

Figure 2

Patterns of colitis in mouse IBD models. Top left, mild proliferative colitis. Top right, moderately severe colitis with extensive crypt epithelial proliferation. Bottom left, severe colitis with partial loss of crypt and superficial epithelium. Bottom right, extremely severe colitis with complete epithelial loss and fibrinous surface exudate. Scoring systems should be designed to appropriately evaluate colitis in which epithelial changes cannot be scored because of epithelial destruction.

Figure 3

Colitis induced by Helicobacter hepaticus in an immunodeficient mouse, with proliferating epithelium penetrating the muscularis mucosa and extending into the submucosa, a nonneoplastic change occurring in chronic severe colitis induced by this organism.