Animal technicians reported a 16-week-old female B6;129S2-Tnfsf5tm1Imx mouse for a primary complaint of cachexia. Clinical signs included lethargy, trembling, low body temperature, anorexia, and weight loss. The animal's body weight was less than 14 g. We subsequently euthanized the mouse by CO2 administration and submitted it for necropsy.

After receiving this mouse from the supplier (Jackson Laboratories, Bar Harbor, ME), we had housed it at a barrier facility in an individually ventilated polycarbonate microisolator cage (Thoren Caging Systems, Inc., Hazleton, PA). Husbandry procedures within the barrier facility included autoclaving of the microisolator cage after washing, supplying autoclaved bedding (ALPHA-dri, Shepherd, Watertown, TN) and autoclaved water bottles, and allowing ad libitum access to water and irradiated feed (7913; Harlan Teklad, Madison, WI). The animal was on study and was receiving intraperitoneal injections of corn oil. The animal technicians also reported that a cagemate of this animal was showing poor weight gain. We provide mice that become lethargic or cachexic during a study with Transgenic Dough Diet (Bio-Serv, Frenchtown, NJ) ad libitum. HEPA-filtered air at 15 air changes per hour supplied the room housing the mice; the cage system (Thoren) moved room air through a HEPA filter into the animal cages, and cage air pressure was positive with respect to the room. We monitored the specific pathogen-free status of the barrier facility by quarterly necropsy and comprehensive serology of sentinel animals exposed to used bedding, feed, and water bottles. Surveillance mice were negative by culture for murine bacterial pathogens and negative for Helicobacter spp. by PCR; we found no helminth or protozoal parasites in surveillance mice.

Gross necropsy of the cachectic female B6;129S2-Tnfsf5tm1Imx mouse showed minimal contents to be present in the gastrointestinal tract and scant, hard feces present in the colon. Multiple tissue samples were fixed in Prefer (Anatech Ltd., Battle Creek, MI), a formalin-free fixative of glyoxal, in a buffered mixture of water and ethanol. We then submitted tissues for histopathological examination.

What do you expect the results of the histopathological examination will be? What do you think caused this mouse to become cachexic?

What's your diagnosis?