Ray Maria A, Johnston Nancy A, Verhulst Steven, Trammell Rita A, Toth Linda A
Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
J Am Assoc Lab Anim Sci. 2010 May;49(3):282-8.
The goal of this study was to identify objective criteria that would reliably predict imminent death in aged mice. Male and female ICR mice (age, 8 mo) were subcutaneously implanted with an identification chip for remote measurement of body temperature. Mice then were weighed and monitored regularly until spontaneous death occurred or until euthanasia was administered for humane reasons. Clinical signs that signaled implementation of euthanasia included inability to walk, lack of response to manipulation, large or ulcerated tumors, seizures, and palpable hypothermia. In mice that died spontaneously, gradual weight loss was the most frequent and earliest sign of imminent death. Hypothermia developed during the 2 wk prior to death. Slow or labored breathing were observed in about half of the mice before death. A composite score of temperature x weight can be used to provide an objective benchmark to signal increased observation or euthanasia of individual mice. Such assessment may allow the collection of terminal tissue samples without markedly altering longevity data, although application of this criterion may not be appropriate for all studies of longevity. Timely euthanasia of mice based on validated markers of imminent death can allow implementation of endpoints that alleviate terminal distress in aged mice, may not significantly affect longevity data, and can permit timely collection of biologic samples.
本研究的目的是确定能够可靠预测老年小鼠即将死亡的客观标准。将雄性和雌性ICR小鼠（8月龄）皮下植入识别芯片，用于远程测量体温。然后对小鼠进行称重并定期监测，直至其自然死亡或因人道原因实施安乐死。表明实施安乐死的临床体征包括无法行走、对操作无反应、肿瘤大或溃疡、癫痫发作以及可触及的体温过低。在自然死亡的小鼠中，体重逐渐减轻是即将死亡最常见和最早出现的体征。体温过低在死亡前2周出现。约一半的小鼠在死亡前出现呼吸缓慢或困难。体温×体重的综合评分可用于提供一个客观基准，以提示增加对个体小鼠的观察或实施安乐死。这样的评估可能允许在不显著改变寿命数据的情况下采集终末组织样本，尽管该标准的应用可能不适用于所有寿命研究。基于已验证的即将死亡标志物对小鼠进行及时安乐死，可以实现减轻老年小鼠终末痛苦的终点，可能不会显著影响寿命数据，并可允许及时采集生物样本。
