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

High and variable pre-weaning mortality is a persistent problem among the main mouse strains used in biomedical research. If a modest 15% mortality rate is assumed across all mouse strains used in the EU, approximately 1 million more pups must be produced yearly to compensate for those which die. A few environmental and social factors have been identified as affecting pup mortality, but optimizing these factors does not cease the problem. This study is the first large study to mine data records from 219,975 pups from two breeding facilities to determine the major risk factors associated with mouse pre-weaning mortality. It was hypothesized that litter overlap (i.e. the presence of older siblings in the cage when new pups are born), a recurrent social configuration in trio-housed mice, is associated with increased newborn mortality, along with high mother age, large litter size, as well as a high number and age of older siblings in the cage. The estimated probability of pup death was two to seven percentage points higher in cages with compared to those without litter overlap. Litter overlap was associated with an increase in percentage of litter losses of 19% and 103%, respectively, in the two breeding facilities. Increased number and age of older siblings, high mother age, small litter size (less than four pups born) and large litter size (over 11 pups born) were associated with increased probability of pup death. Results suggest that common social cage configurations at breeding facilities are dangerous for the survivability of young mouse pups. The underlying mechanisms and strategies to avoid these situations should be further investigated.