Practical pathology of aging mice

Pettan-Brewer, Christina; Treuting, Piper M.

The mouse rectum, in contrast to the human, is extremely short and is susceptible to prolapse. Rectal prolapse ( Fig. 1 ) in mice may be caused by inflammation in the colon due to infectious agents, such as pinworms or Helicobacter species (Fig. 1CÁF) , with increased abdominal pressure caused by pregnancy, masses, stranguria, or diarrhea. With age, it is plausible that the pelvic musculature may weaken allowing for prolapses to occur more readily Á although this has not been investigated extensively (24) . In many cases, the definitive cause for rectal prolapse is not determined; however, known causes may be excluded. In the UW aging colonies, pinworms and Citrobacter rodentium have not been diagnosed. The colonies are not tested for Helicobacter species, which can cause colitis and rectal prolapse in certain susceptible GEMs such as the 129-Smad3 tm/Par /J model of bacterialdriven colon cancer (14) . In immune competent mice, such as B6, Helicobacter species are considered commensal and should not cause disease. Rectal prolapses vary in clinical appearance (Fig. 1BÁD ) and, in female mice, must be distinguished from uterine or vaginal prolapse. Mild prolapse is a protrusion of the rectum extending only 1Á2 mm from the base of the tail and perineum and the prolapsed mucosa is light pink and moist, with little adherent material (Fig. 1B) . Mild prolapse often cause little detriment to the animal, which can survive and thrive with these lesions for some time. Severe rectal prolapse is a protrusion of both distal colon (DC) and rectal mucosa extending !3 mm from the base of the tail and perineum (Fig. 1C,D) . The severely prolapsed mucosa is often reddened and edematous to necrotic with adhered fecal or bedding material (Fig. 1C) . Often, feces inside the cage will be sticky, an indication of diarrhea. In long-standing cases, the mucosa may become proliferative (Fig. 1D) . Exposure of the delicate colorectal mucosa to the cage environment provides a nidus of chronic inflammation and entry of bacteria in the systemic circulation. There is no completely effective treatment for rectal prolapse. Clinical recommendations for mice with rectal prolapses vary between facilities and experimental protocols; in general, mild rectal prolapses with no other clinical signs of systemic illness are often monitored, while euthanasia is recommended for mice with moderate to severe rectal prolapses. Histologically, the prolapsed mucosa may be ulcerated to necrotic or, with chronicity, proliferative with squamous metaplasia (Fig. 1E,F) . Adherent bacterial colonies, plant material and fecal matter may also be present. In typical cases, the underlying vasculature and submucosa (SM) is edematous and inflamed and may be congested. Inflammation may be acute, primarily neutrophilic when there are ulcers and bacteria, or lympho- Fig. 3 . Clinical and histological presentations of common eye lesions. A. Normal periocular shape, eye size, and color in a 24-monthold CB6F1 mouse included here for contrast to the mouse in 3B. Note the lack of pelage and vibrissae due to extensive barbering by cage mates. Barbering is another relatively common skin presentation. It may lead to dermatitis in the victim and impaction of hair fragments into gingival sulcus of the barber. B. A 24-month-old CB6F1 mouse has periocular and retrobulbar swelling (between arrows) with bulopthalmia. This presentation may be a result of periocular cellulitis, conjunctivitis, or retrobulbar mass su