Granulomatous peritonitis and pleuritis in interferon‐γ gene knockout mice naturally infected with mouse hepatitis virus

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Abstract
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 immunohistochemistry. Affected mice exhibited depression and variable ascites. Necropsy revealed a granulomatous peritonitis and pleuritis with extensive adhesions although parenchymal lesions were minimal. Serum samples had high concentrations of antibody to mouse hepatitis virus and immunohistochemical examination revealed the presence of mouse hepatitis virus antigen in granuloma macrophages. Sero-logical testing for other infectious agents and bacterial culture were negative and wild type mice kept in the same facility remained healthy. Despite the association between the disease and mouse hepatitis virus infection, the precise role played by mouse hepatitis virus was not determined. While the disease is superficially similar to feline infectious peritonitis (another coronavirus-induced serositis), differences exist between the histopathological findings in these two conditions. This unusual disease process illustrates how new diagnostic challenges can arise in novel mouse genotypes created through molecular genetics. Furthermore, the association between the disease and mouse hepatitis virus illustrates the importance of maintaining laboratory animals under specific-pathogen free conditions.