Short Specialist Review Imprinting and behavior

1. Evidence for the role of imprinted genes in behavioral phenotypes The crossbreeding of animal species with one another can often produce hybrids with parent-of-origin-specific changes in behavioral phenotypes. For instance, the offspring of a male zebra and a female donkey are noted for their stubbornness in comparison with the reciprocal cross (Gray 1972; Walton & Hammond 1938). For many years, it was unclear why these genetically equivalent individuals behaved in consistently different ways dependent upon parent of origin. Following the discovery of genomic imprinting, it is now acknowledged that these offspring differ in their expression of imprinted genes and that differences in the maternal and paternal alleles of reciprocal crosses at these loci could lead to the observed behavioral differences. Hybrid F1 mice produced from mating a male from an inbred strain A and a female from inbred strain B can be compared with those produced from the reciprocal cross. If both sets of offspring are transferred as embryos into a different strain C, these offspring are genetically equivalent in every respect with the exception of their imprinted genes. Interestingly, it was found that reciprocal cross F1 offspring avoid female urine from their maternal strain and investigate more the urine from an unrelated strain D in a choice test (Isles et al ., 2001). However, no preference was observed when these mice were given the opportunity to investigate female urine from either a neutral strain D or their genetic paternal strain. This finding has been replicated with at least two separate parental sets of inbred strains, demonstrating that the effect of imprinted genes on mate choice is likely to be universal and not an epiphenomenon of one particular inbred strain (Isles et al ., 2002). Moreover, since the F1 offspring were embryo transferred to foster mothers of a separate strain, this eliminated the possibility that the avoidance of maternal strain odors was dependent upon any learning during pup development. The importance of genomic imprinting in brain and behavioral development was further illustrated by identifying where in the brain cells expressing imprinted genes preferentially develop (Allen et al ., 1995; Keverne et al ., 1996a). Mice with two complete sets of maternal or paternal chromosomes were only viable until day 10 of gestation (see Article 28, Imprinting and epigenetics in mouse models and embryogenesis: understanding the requirement for both parental