Causes of death in newborn C57BL/6J mice

Abstract

22Neonatal mortality in wild-type laboratory mice is an overlooked welfare and financial 23 problem in animal facilities around the world. Causes of death are often not reported 24 and its causes remain unknown. 25 In this study, 324 newborn pups from two breeding colonies of healthy wildtype 26 C57BL/6 mice underwent post-mortem analysis with special focus on obtaining proof 27 of life after birth, evaluation of stomach contents and observation of congenital 28 abnormalities that could compromise survival. 29 Based on a combination of lung morphology findings, outcome of lung float test, 30 stomach contents and brown adipose tissue colouration, 21.6% of the pups found 31 dead were considered stillbirths. Of the livebirths, only 3.2% were observed to have 32 milk inside the stomach, indicating successful suckling. Congenital abnormalities were 33 diagnosed only in a small fraction of the pups analysed. These results suggest that 34 starvation was the most common cause of death, followed by stillbirth. 35 Keywords 36Neonatal mortality, Mouse, causes of death, C57BL/6J 37 High rates of pre-weaning mortality in laboratory mice are a widespread issue among 38 animal facilities worldwide. This represents a major welfare problem 33 , a significant 39 financial burden through lowered productivity and has an impact on the 3Rs by 40 increasing the number of animals needed and used for breeding. 41Rates of perinatal mortality are reported as higher in inbred strains, especially in 42 C57BL/6 mice, where they can reach 50% 19 . Attention to morbidity and mortality in 43 newborn mice occurs primarily in the context of phenotyping genetically modified 44 mice 2, 29, 45 . In contrast, knowledge about causes of neonatal death in breeding 45 colonies of healthy wildtype mice is limited and currently there are no agreed published 46 guidelines or strategies to address this issue. 47 Mice are an altricial species and pups are dependent on parental care within a 48 maternal nest during the first phase of their lives. The pups are born helpless, relatively 49 immobile, blind, hairless, capable of suckling but not able to otherwise fend for 50 themselves. They possess a very limited ability to produce heat by non-shivering 51 thermogenesis using brown adipose tissue (BAT) 6, 18 . Consequently, major causes of 52 neonatal mortality and low viability could be related to failures of parental care, such 53 as predation, starvation and hypothermia in addition to birthing accidents, congenital 54 defects and infectious processes.55Wild mice are communal nesters and females often share duties in the care for the 56 young 49 . This characteristic is maintained in laboratory mice and is often exploited by 57 housing mice in breeding trios, which allows for increases in the number of pups per 58 cage 47 and individual pup growth 15, 16 . However, this social conformation is more prone 59 to litter overlap 3 , the existence of a previous litter inside the cage, which is associated 60 with higher neonatal mortality 3 . 61There is a ...

High laboratory mouse pre-weaning mortality associated with litter overlap, advanced dam age, small and large litters

“…Most often, when there are two females sharing a cage, they also share the same nest, and younger lighter pups get clustered together with the older, heavier, and more mobile pups. Data on post-mortem inspection performed in 324 C57BL/6J pups found dead, by the authors of this study, revealed that 24% of the pups had some kind of traumatic lesion, including bite wounds and bruises [25].…”

Mouse helpers ensure maternal-infant survival

“…Parental animals must balance caregiving behaviors with other behaviors required for their own survival, making single parenting especially challenging. Previous studies of rodents and other species report a remarkably high degree of infant mortality, both outdoors in native habitats and animals housed in laboratory conditions-although it remains controversial how much infant mortality occurs for isolate vs communally-rearing mothers (König, 1993; Manning et al, 1995; Ferrari et al, 2019; Capas-Peneda et al, 2020; Brajon et al, 2021). We aimed to resolve when and how pup mortality occurs, if it is due to parental neglect or other factors, and if mouse mothers might learn from certain experiences to improve maternal care over subsequent litters.…”

Bibliometric analysis on cannibalism/infanticide and maternal aggression towards pups in laboratory rodents

“…Consequently, there is decreased breeding performance, which has been associated with a reduced welfare in laboratory rodents. [1][2][3][4] Although the mortality rate reported in laboratory mice is high, there is limited knowledge on how pups die. Investigating the different reasons which lead to pups' death is the key to preventing a lower performance in mouse reproduction.…”

“…Consequently, there is decreased breeding performance, which has been associated with a reduced welfare in laboratory rodents. 1 –4…”