小鼠繁殖中断奶前的高死亡率是困扰全球实验室的重要问题之一，其一方面严重影响动物福利，另一方面也会造成很大的经济损失。据以往研究报告，C57BL/6幼鼠死亡率从小于10%到高达49%^[1-3]。假设保守估计各小鼠品系的死亡率为15%，仅欧盟来说，每年就至少要多生产100万只小鼠以补偿死去的小鼠幼崽以用于科学研究^[4]。尽管研究人员依据3R原则，正努力提高幼鼠的存活率及福利，但高断奶前死亡率仍然存在。2020年，波尔图大学研究者在 PLOS ONE杂志上发表题为“High laboratory mouse pre-weaning mortality associated with litter overlap, advanced dam age, small and large litters”的文章，报道了通过大规模系统研究发现与实验室小鼠断奶前高死亡率相关的危险因素^[5]。

研究分析了来自两个繁育设施219,975只小鼠幼崽的历史信息，包括每窝幼崽出生和断奶时的数量、亲代年龄和身份确认及所有动物出生和死亡日期等。采用两种统计模型，揭示了实验小鼠的高断奶前死亡率与母鼠年龄增大（advanced dam age）和同窝幼崽的数量(少于4只或超过11只)相关，据推测同窝幼崽数量过多导致存活率降低与争夺母乳相关，而幼崽数量过少可能与不易抱团维持体温和不能发出足够大的声音获得母亲及时照料相关。除此之外，由同一母亲生产但不同窝小鼠同笼饲养（litter overlap）时新生幼崽存活率会降低，并且与笼中前几窝小鼠的数量和年龄密切相关，笼中年龄较长小鼠数量越多、周龄越大都与幼鼠死亡率呈正相关，亲代抚育行为、子代小鼠间争夺母乳都可能是导致幼鼠死亡的原因。研究还特别提到，幼崽主要是由于相互踩踏、争抢不到母乳或未得到足够照料等导致死亡，死亡后会发生同类相食（cannibalism）现象，其发生比例高于以往认为的杀婴行为（infanticide，直接杀死幼崽）^[5-6]。

参考文献：

1. Reeb-Whitaker CK, Paigen B, Beamer WG, Bronson RT, Churshill GA, Schweitzer IB, et al. The impactof reduced frequency of cage changes on the health of mice housed in ventilated cages. Lab Anim.2001. 35:58–73.

2. Gaskill BN, Pritchett-Corning KR, Gordon CJ, Pajor EA, Lucas JR, Davis JK, et al. Energy reallocationto breeding performance through improved nest building in laboratory mice. PLoS One. 2013. 8(9):e74153.

3. Inglis CA, Campbell ER, Auciello SL, Sarawar SR. Effects of Enrichment Devices on Stress-Related Problems in Mouse Breeding. Johns Hopkins Cent Altern to Anim Test Final Rep Anim Welf Enhanc Award 2004..(1):1–9.

4. European Commission. 2019 report on the statistics on the use of animals for scientific purposes in the member states of the European Union in 2015–2017. 2020 Feb 5. Brussels. Available from: https://eur-lex.europa.eu/legal-content/EN/.

5. Gabriela M Morello , Jan Hultgren , Sara Capas-Peneda,et al.High laboratory mouse pre-weaning mortality associated with litter overlap, advanced dam age, small and large litters. PLoS One. 2020.15(8): e0236290.

6. Sophie Brajon, Gabriela Munhoz Morello , Sara Capas-Peneda , et al. All the Pups We Cannot See: Cannibalism Masks Perinatal Death in Laboratory Mouse Breeding but Infanticide Is Rare. Animals 2021(11): 2327.