Proliferative Typhlocolitis With Multinucleated Giant Cells: A Nonspecific Enteropathy in Immunodeficient Sentinel Mice.

Beginning in 2015, athymic nude sentinel mice from conventional, medium-, and high-security facilities presented to the Comparative Pathology Laboratory (CPL) with weight loss, diarrhea, and/or rectal prolapse. Regardless of whether clinical signs were present or absent, the gross observation of ceco-colonic thickening corresponded histologically to pleocellular typhlocolitis with mucosal hyperplasia and lamina proprial multinucleated cells. A subset of affected sentinels exhibited granulomatous serositis and hepatosplenic necrosis with multinucleated cells. Initial suspicion of mouse hepatitis virus infection was excluded by polymerase chain reaction, electron microscopy, and serology. Multinucleated giant cells were confirmed as macrophages by positive immunoreactivity to Mac-3 and Iba-1 and negative immunoreactivity to pancytokeratin. From conventional and medium-security facilities, Helicobacter species were identified in 40 of 143 (27.9%) mice, with H. hepaticus accounting for 72.5% of identified Helicobacter species. Other agents included opportunistic bacterial infection (41/145, 28.3%), murine norovirus (16/106, 15.1%), and pinworms (2/146, 1.4%). From high-security facilities, only Enterobacter cloacae was identified (2/13, 15.4%), and no evidence of Helicobacter sp., murine norovirus, or pinworms was present. No potentially infectious disease agent(s) was identified in 71 of 146 (48.6%) affected nude sentinels from conventional and medium-security facilities and 11 of 13 (84.6%) affected nude sentinels from high-security facilities. No statistically significant differences in histologic lesion scores were identified between Helicobacter-positive and Helicobacter-negative mice. Thus, proliferative typhlocolitis with multinucleated giant cells was considered a nonspecific histologic pattern associated with a variety of primary and opportunistic pathogens in athymic nude mice.

Mousepox detected in a research facility: case report and failure of mouse antibody production testing to identify Ectromelia virus in contaminated mouse serum.

An outbreak of mousepox in a research institution was caused by Ectromelia-contaminated mouse serum that had been used for bone marrow cell culture and the cells subsequently injected into the footpads of mice. The disease initially was diagnosed by identification of gross and microscopic lesions typical for Ectromelia infection, including foci of necrosis in the liver and spleen and eosinophilic intracytoplasmic inclusion bodies in the skin. The source of infection was determined by PCR analysis to be serum obtained from a commercial vendor. To determine whether viral growth in tissue culture was required to induce viral infection, 36 mice (BALB/cJ, C57BL/6J) were experimentally exposed intraperitoneally, intradermally (footpad), or intranasally to contaminated serum or bone marrow cell cultures using the contaminated serum in the culture medium. Mice were euthanized when clinical signs developed or after 12 wk. Necropsy, PCR of spleen, and serum ELISA were performed on all mice. Mice injected with cell cultures and their cage contacts developed mousepox, antibodies to Ectromelia, and lesions, whereas mice injected with serum without cells did not. Mouse antibody production, a tool commonly used to screen biologic materials for viral contamination, failed to detect active Ectromelia contamination in mouse serum.