Parent-of-origin Effects on Behavior and Development in Reciprocal Hybrid Mice

James Curley
Sub-Department of Animal Behaviour; University of Cambridge

Genomic imprinting and maternal programming are two epigenetic mechanisms through which variations in offspring behavioral and physiological phenotype may arise [1,2]. We are currently establishing mouse models to investigate the role of these mechanisms in the development of behavioral phenotypes in offspring. In this study, we characterized differences in the postpartum maternal care of two strains of inbred mice and investigated the behavior and development of reciprocal crosses of these strains. We found that 129Sv dams exhibit high levels of nursing and low levels of licking/grooming (LG) towards offspring, with B6 dams showing the reverse pattern. The reciprocal hybrids of these inbred strains also differ in their maternal care in a parent-of-origin specific manner, with F1-129SvB6 dams exhibiting significantly less pup LG than F1-B6129Sv dams. Both male and female hybrids also exhibited other behavioral differences in a parent-of-origin specific manner, with F1-129SvB6 mice being more anxious and less exploratory than F1-B6129Sv mice. Finally, F1-129SvB6 mice were larger at weaning and pre-puberty compared to F1-B6129Sv, but this weight difference was not observed in adulthood, suggesting the possibility of epigenetic regulation of body weight and metabolic pathways. We are currently extending this study by using a cross-fostering paradigm to discern whether the differences in phenotype observed between reciprocal hybrids are the result of maternal programming, imprinting, both or some other mechanism. Using these strain differences in growth and behavior as a model, our future goals are to identify the genes encoding neuropeptide and hormone receptors that are targets of epigenetic regulation and to investigate the levels of genomic imprinting between these strains and their reciprocal hybrids. (JPC is supported by the Cambridge-Leverhulme Initiative in Post-Genomics Research and FAC is funded by a fellowship from the Canadian Institutes of Health Research (CIHR). Work was supported by a BBSRC grant to EBK).


  1. Curley, JP, Barton, S, Surani, A, and Keverne EB: Coadaptation in mother and infant regulated by a paternally expressed imprinted gene. Proc Biol Sci 271: 1303-1309, 2004.

2.Weaver, IC, Cervoni, N, Champagne, FA, D'Alessio, AC, Sharma, S, Seckl, JR, Dymov, S, Szyf, M, and Meaney ,MJ. Epigenetic programming by maternal behavior. Nat Neurosci 7: 847-854, 2004.