Spontaneous, heritable colitis in a new substrain of C3H/HeJ mice.

Background/aims: C3H/HeJ mice at the Jackson Laboratory have periodically been culled because of the occurrence of soft feces, perianal ulceration, and right-sided colitis. No pathogens have been isolated. The goal of the current study was to establish a substrain with a high incidence of this disease.

Methods: Affected male and female C3H/HeJ mice were bred. The clinical, pathological, microbiological, and genetic features of 216 mice of the resulting pedigree were characterized.

Results: A severely affected female crossed with a normal male resulted in a new substrain, denoted C3H/HeJBir, with a high incidence of right-sided colitis. Histologically, lesions occurred primarily in the cecum and proximal colon, characterized by acute and chronic inflammation, crypt abscesses, ulcerations, regenerative hyperplasia, and submucosal scarring. Such colitis peaked at 3-6 weeks; however, similar disease was found sporadically in animals more than 1 year of age. Small lesions at the anorectal junction were common throughout life. An extensive search for pathogens was negative. Genetic analysis of C3H/HeJBir mice suggested that the disease was inherited as a quantitative trait.

Conclusions: C3H/HeJBir mice develop a spontaneous, heritable form of idiopathic inflammatory bowel disease and will be a valuable resource for genetic and immunologic studies of this disease.