Practical pathology of aging mice

Pettan-Brewer, Christina; Treuting, Piper M.

Clinical assessments and definitions of sick versus moribund mice Clinical observations in mouse colonies typically begin with superficial assessments by the husbandry staff during change changing. These readily conducted assessments include body condition, pelage condition, and activity levels (15, 16) . A general consensus for normal mouse appearance includes a well-kept coat, bright eyes, erect ears, active and engaged in its environment (17) . If an animal deviates from the observer's definition of normal, it is reported to Veterinary Service Staff through generation of a 'sick animal report'. Veterinary service staff and/or clinicians conduct a thorough physical exam and determine the health status of the mouse. Generally accepted sick rodent signs include hunched posture, unkempt coat, discharge from the eyes or other body orifice, rectal or uterine prolapses, skin lesions, palpable masses, reluctance to move, poor body condition, and/or hydration. The presentation of illness and its severity in a mouse can be varied and therefore descriptive criteria for end points must be established in order to minimize pain and distress and maximize data quality (15) . For aging colonies, the mice are ideally maintained until near end of life (EOL) and will have age-associated diseases that may cause some to consider the old mouse 'sick' (18) . To prevent unwarranted censoring of mice due to nonterminal diseases, consensus descriptive criteria for endof-life and humane euthanasia were developed. Mice were considered to be at EOL and euthanized when they were moribund and demonstrated one or more clinical signs suggestive of imminent death within 24 hours (19) . These signs included (1) non-responsiveness to being touched, (2) cold body temperature to the touch, (3) slow or labored respiration, (4) hunched body position with matted fur, (5) failure to eat and drink (as determined by food hopper weights and degree of dehydration), or (6) poor body condition score or !20% loss of body weight relative to baseline (20) . Mice that were nearing EOL, as determined by less severe clinical signs and up to 20% weight loss, were closely examined twice a day, 7 days a week. Mice that met the above criteria were killed by CO 2 and necropsies performed.