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Markers for predicting death as an outcome for mice used in infectious disease research
Rita A Trammell1, Linda A Toth
1Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
Abstract:
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.
Insights
Hypothermia and weight loss are key indicators of mortality in mice infected with various agents. These predictive markers vary by model, emphasizing the need for context-specific validation in research.
Area of Science:
- Veterinary Medicine
- Infectious Disease Research
- Animal Models
Background:
- Predicting mortality in experimental infections is crucial for ethical animal research and data integrity.
- Objective endpoint criteria are needed to standardize the assessment of disease progression and outcome in animal models.
Purpose of the Study:
- To identify objective criteria for predicting mortality in mice following experimental inoculation with infectious agents.
- To evaluate the utility of physiological parameters like body temperature and weight as predictive markers for survival or death.
Main Methods:
- Retrospective analysis of data from four independent studies involving different infectious agents (influenza, Streptococcus pneumoniae, Candida albicans) and mouse strains.
- Remote monitoring of body temperature via implanted microchips or radiofrequency transmitters.
- Regular monitoring of body weight and temperature until death or euthanasia.
Main Results:
- Hypothermia was the most significant predictor distinguishing between surviving and non-surviving mice across models.
- Weight loss was also a useful, though variable, indicator of outcome.
- A combined measure of temperature and body weight product showed utility in some models, but effectiveness varied substantially by experimental setup.
Conclusions:
- No single endpoint marker is universally applicable across different animal infection models.
- Predictive markers for mortality must be developed and validated within the specific context of the experimental model being used.
- Validated markers can facilitate timely euthanasia, reducing animal distress and enabling efficient sample collection.
