Hull Margaret A, Reynolds Penny S, Nunamaker Elizabeth A
Animal Care Services, University of Florida, Gainesville, Florida, United States of America.
Department of Anesthesiology; Statistics in Anesthesiology Research (STAR) Core, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
PLoS One. 2022 Jan 28;17(1):e0263192. doi: 10.1371/journal.pone.0263192. eCollection 2022.
Non-aversive handling is a well-documented refinement measure for improving rodent welfare. Because maternal stress is related to reduced productivity, we hypothesized that welfare benefits associated with non-aversive handling would translate to higher production and fewer litters lost in a laboratory mouse breeding colony. We performed a randomized controlled trial to examine the effects of a standard method of handling (tail-lift with forceps) versus non-aversive handling with transfer tunnels ('tunnel-handled') on breeding performance in 59 C57BL/6J mouse pairs. Intervention assignments could not be concealed from technicians, but were concealed from assessors and data analyst. An operationally significant effect of tunnel-handling (large enough differences to warrant programmatic change) was defined before study initiation as a 5% increase in productivity, or one extra pup over the reproductive lifetime of each pair. Pairs were randomly allocated to handling intervention and cage rack location, and monitored over an entire 6-month breeding cycle. For each group, we measured number of pups born and weaned, and number of entire litters lost prior to weaning. Differences between transfer methods were estimated by two-level hierarchical mixed models adjusted for parental effects and parity. Compared to tail-lift mice, tunnel-handled mice averaged one extra pup per pair born (+1.0; 95% CI 0.9, 1.1; P = 0.41) and weaned (+1.1, 95% CI 0.9, 1.2; P = 0.33). More tunnel-handled pairs successfully weaned all litters produced (13/29 pairs, 45% vs 4/30 pairs, 13%; P = 0.015), averaged fewer litter losses prior to weaning (11/29 pairs [38%] vs 26/30 pairs [87%]; P <0.001), and had a 20% lower risk of recurrent litter loss. The increase in numbers of pups produced and weaned with tunnel handling met threshold requirement for operational significance. These data and projected cost savings persuaded management to incorporate tunnel handling as standard of care across the institution. These data also suggest that overlooked husbandry practices such as cage transfer may be major confounders in studies of mouse models.
非厌恶式操作是一种有充分文献记载的改善啮齿动物福利的优化措施。由于母鼠应激与繁殖力下降有关，我们推测与非厌恶式操作相关的福利改善将转化为实验室小鼠繁殖群体更高的繁殖量和更少的窝仔丢失。我们进行了一项随机对照试验，以检验标准操作方法（用镊子提起尾巴）与使用转移通道的非厌恶式操作（“通道操作”）对59对C57BL/6J小鼠繁殖性能的影响。技术人员无法隐瞒干预分配情况，但评估人员和数据分析师对此不知情。在研究开始前，将通道操作的具有实际意义的效果（差异大到足以保证进行方案变更）定义为繁殖力提高5%，即每对小鼠在整个繁殖期多产一只幼崽。将小鼠对随机分配到操作干预组和笼架位置，并在整个6个月的繁殖周期内进行监测。对于每组，我们测量出生和断奶的幼崽数量，以及断奶前整窝丢失的数量。通过调整亲本效应和胎次的两级分层混合模型估计转移方法之间的差异。与提尾小鼠相比，通道操作的小鼠每对平均多产一只幼崽（+1.0；95%置信区间0.9，1.1；P = 0.41），断奶幼崽数量也更多（+1.1，95%置信区间0.9，1.2；P = 0.33）。更多接受通道操作的小鼠对成功断奶了所有产仔（13/29对，45%对4/30对，13%；P = 0.015），断奶前平均窝仔丢失更少（11/29对[38%]对26/30对[87%]；P <0.001），且反复窝仔丢失风险降低20%。通道操作使产仔和断奶幼崽数量的增加达到了实际意义的阈值要求。这些数据和预计的成本节约促使管理层将通道操作纳入整个机构的护理标准。这些数据还表明，诸如笼具转移等被忽视的饲养操作可能是小鼠模型研究中的主要混杂因素。
