Research into neonatal vitality in laboratory mouse breeding

This research is coordinated by Anna Olsson in collaboration with Gabriela Morello and Sara Capas Peneda.

Better understanding of the mechanisms behind early pup mortality, including determining cause of death, is important to be able to develop preventive measures. We work together with researchers at Babraham Institute (UK) and the Francis Crick Institute (UK) and at the Swedish University of Agricultural Sciences (Sweden).

Photo: Sophie Brajon

High preweaning mortality in laboratory mouse breeding is a major welfare and economic problem worldwide. Literature reports pup mortalities varying from <10% to 49% for the commonly used C57BL/6 strain. Despite greater environmental protection, preweaning mortality in mice is substantially higher than for food production animals: in pigs, a comparable litter-bearing mammal, mortality ranges around 5-15%.

In the first large multi-site study under practice conditions we showed that mortality varies greatly between facilities and is substantially larger than reference data. In data from 35,000 litters of C57BL/6 mice we found 39% preweaning mortality in one facility and 14% in the other, whereas reference data is 8%. Translating a conservative 25% neonatal mortality to the EU as a whole means that about 2 million extra mice are needed yearly to compensate for neonatal mortality.

Mice’ nocturnal and nestbuilding nature, and the fact that dead pups are often eaten by the progenitors make mortality challenging to detect and quantify, further complicated by the standard practice of limiting inspection of periparturient females to what can be seen without opening the cage. Pups are often not counted until the first cage change, up to 2 weeks postpartum. We know from our several experiments that most pups die on days 0-3 postpartum, i.e. earlier than the first pup count in many breeding facilities. It is likely that many animal facilities underestimate mortality because newborn pups are missed.

We are using a combination of ethology, epidemiology, data science and pathology in our research into neonatal pup mortality.

Relevant papers

Morello G, Hultgren J, Capas Peneda S, Wiltshire M, Thomas A, Wardle-Jones H, Gilbert C, Olsson IAS. High laboratory mouse pre-weaning mortality associated with litter overlap, advanced mother age, small and large litters. PLoS One. 2020;15(8):e0236290.

Capas-Peneda S, Munhoz Morello G, Lamas S, Olsson IAS, Gilbert C. Necropsy protocol for newborn mice. Laboratory Animals. January 2021. doi:10.1177/0023677220983374

Brajon S, Munhoz Morello G, Teixeira MS, Hultgren J, Gilbert C, Olsson IAS. Social environment as a cause of litter loss in laboratory mouse: A behavioural study. Applied Animal Behaviour Science. 2019;218.

Weber EM, Hultgren J, Algers B, Olsson IAS. Do laboratory mouse females that lose their litters behave differently around parturition? PLoS One. 2016;11(8):e0161238-e

Weber EM, Algers B, Hultgren J, Olsson IAS. 2013. Pup mortality in laboratory mice – infanticide or not? Acta Veterinaria Scandinavica 55:83 doi:10.1186/1751-0147-55-83

Weber EM, Algers B, Würbel H, Hultgren J, Olsson IAS. 2012. Influence of strain and parity on the risk of litter loss in laboratory mice. Reproduction in Domestic Animals. DOI: 10.1111/j.1439-0531.2012.02147.x

Weber EM and Olsson IAS. 2008. Maternal behaviour in Mus musculus: an ethological review. Applied Animal Behaviour Science 114: 1-22.