Granulomatous peritonitis and pleuritis in interferon-gamma gene knockout mice naturally infected with mouse hepatitis virus

Objective To investigate a disease outbreak in a colony of laboratory mice with targeted disruption of the gene for interferon-gamma Format A case report based on necropsy, histopathology, serology and immuno histochemistry. Results Affected mice exhibited depression and variable ascites. Necropsy r evealed a granulomatous peritonitis and pleuritis with extensive adhesions although parenchymal lesions were minimal. Serum samples had high concentra tions of antibody to mouse hepatitis virus and immunohistochemical examinat ion revealed the presence of mouse hepatitis virus antigen in granuloma mac rophages. Sere-logical testing for other infectious agents and bacterial cu lture were negative and wild type mice kept in the same facility remained h ealthy. Despite the association between the disease and mouse hepatitis vir us infection, the precise role played by mouse hepatitis virus was not dete rmined. While the disease is superficially similar to feline infectious per itonitis (another coronavirus-induced serositis), differences exist between the histopathological findings in these two conditions. Conclusion This unusual disease process illustrates how new diagnostic chal lenges can arise in novel mouse genotypes created through molecular genetic s. Furthermore, the association between the disease and mouse hepatitis vir us illustrates the importance of maintaining laboratory animals under speci fic-pathogen free conditions.