Markers for Predicting Death as an Outcome for Mice Used in Infectious Disease Research

Our goal in this study was to identify objective criteria that could be used to predict an outcome of death in mice subjected to experimental inoculation with infectious organisms. We conducted a retrospective analysis of data collected from 4 independent studies that used several infectious agents (influenza virus strains A/HK/x31[H3N2] and A/Puerto Rico/8/34[H1N1], Streptococcus pneumoniae, and Candida albicans) and mouse strains (A/J, DBA/2J, C57BL/6J, BALB/cByJ). Postinoculation periods ranged from 5 to 21 d, with survival of 30% to 60% of the subjects. In all studies, mice were implanted with either a subcutaneous identification microchip or an intraabdominal radiofrequency transmitter to allow remote measurement of body temperature. After inoculation, mice were weighed and monitored regularly until death occurred or euthanasia was performed. Hypothermia was the most valuable characteristic for distinguishing mice that would survive or succumb to the infection. In addition, weight loss was useful in some of the models. In some cases, the derived measure of the product of temperature and body weight provided the best differentiation of mice in the 2 outcome categories. Therefore, the utility of these measures varied substantially depending on the specific model. This study demonstrates that specific endpoint markers are not uniformly applicable to different models. Rather, such markers should be developed and tested in the context of the model in which they will be used. The use of validated markers for eventual death can signal the need for preemptive euthanasia to alleviate terminal distress and permit timely collection of biologic samples.