Projecto nº:016591

Referência do Projecto:PTDC/CVT-WEL/1202/2014 (POCI-01-0145-FEDER-016591)

Título:Perinatal mortality in laboratory rodents

Montante envolvidos:

Investimento total: 199.434,00€

IBMC-Instituto de Biologia Molecular e Celular - 199.434,00€

Apoio FEDER: 169.518,90€

Apoio OE: 29.915,10€

Localização do projecto: Porto, Portugal

Sintese do projecto:

The mouse is the predominant model organism in research: nearly 60% of all animals used for experimental purposes in Europe are mice. A great number of these are genetically modified, and a typical laboratory animal facility may keep hundreds of breeding colonies of mice with different genetic backgrounds. Breeding efficiency is often hampered by reproductive problems. Often the whole litter is lost, thus seriously affecting the logistics of animal breeding with subsequent economic consequences of having to keep larger numbers of breeding animals. High pup mortality is cause for particular concern as this is also an animal health and welfare issue. Understanding factors underlying pup mortality is a key to developing preventive strategies, which would improve animal welfare and decrease the number of breeding animals needed to provide experimental animals. In this study we propose to combine epidemiological and ethological methods to map risk factors and understand the course of events that lead to pup death and subsequently to present a prevention strategy. Mortality varies between facilities and strains; our own data indicate 30-35% early pup mortality for C57BL/6 mice

which is the most common strain both in its own right and as background strain for genetic modifications. Despite the size of the problem, there has been very little scientific research into the phenomenon and its underlying factors. In most cases, neither the direct cause of death nor the events leading up to it are known. Existing literature gives a scattered picture of pup mortality, with great variability between different studies. In experimental studies a number of factors have been found to affect pup survival. However, these factors have been addressed in single studies with a great variation in methodology, limiting the possibility to draw general conclusions. In addition, although pup mortality is often attributed to inappropriate mothering ability, this has not been based on detailed comparative analysis of maternal behaviour. The proposed study is the first comprehensive large-scale systematic study of perinatal mortality in mouse breeding. It builds on methods developed within our previous research and will be run in collaboration with nationally leading animal facilities as well as a multinational commercial laboratory animal supplier. Early pup mortality in mice is likely to have a complex background, involving factors related to animal husbandry interacting with genetic effects. Epidemiology has proven a powerful and non-invasive approach to understanding the background of multifactorial problems of this type. Using an epidemiologic approach, we aim to identify potential risk factors of pup loss and to test the effect of experimentally controlling these factors. In the first task, laboratory mouse breeding routines and mortality will be mapped across breeding facilities in Portugal, Sweden and the UK. Data will be collected through interviews with facility managers to obtain a detailed picture of animal environment, management routines and pup mortality in mouse breeding facilities, as well as a list of key risk factors for mortality which are possible to control or manipulate at individual facilities. In the second task, we will assess the impact of the risk factors identified in the previous task, through a controlled interventive study at three selected breeding facilities. This allows introducing or exploring existing variation in risk factors and extensive and reliable collection of complete and standardised data in order to obtain detailed information about the effect of factors that are associated with a high risk of litter loss. In the third task an ethological study will be carried out based on video recordings collected in the previous task. A random sample of breeding cages will be video recorded and from these recordings, comparisons will be made between females losing their litter and females successfully bringing their litter to weaning. Detailed behavioural observations will be carried out from these recordings to identify whether the pups are actively killed by the female and to identify key differences in maternal behaviour between females losing or successfully raising their litter.

The fourth task will analyze clinical data on the cause of pup death. From the animal breeding monitored in Task 2, pups that are found dead and not eaten will be collected from a randomly selected number of litters and subject to post mortem analysis. Gross pathology examination in situ will be combined with histopathological analysis. Based on the results of the described studies, a preventive strategy will be proposed and presented to the laboratory animal science community (Task 5). This project will provide detailed understanding of pup mortality and underlying risk factors and propose recommendations for enhancing pup survival.

Galeria de fotos do projeto