Of particular significance however, is the association of the early poor feeding and failure to thrive phenotype with restricted production of bioactive oxytocin (OT) in the hypothalamus of Magel2 KO new-borns [21]. Among other functions, OT is an anorexigenic hormone which effects feeding control and this led the researchers to test a possible intervention strategy. A single Topoisomerase inhibitor injection of OT before the first 5 hours

after birth completely rescued the early mortality by the recovery of normal suckling in Magel2 KO new-borns [21]. Early administration of OT is now a potentially promising therapeutic for the early failure to thrive and feeding problems seen in PWS newborns. A fascinating recent example of an imprinted gene impacting upon brain and behaviour is that of the gene encoding the growth factor receptor-bound protein 10 (Grb10). Behavioural studies of mice with a paternally inherited null Grb10 (Grb10+/p) demonstrated a role for this gene in social dominance behaviour

[22]. The ‘tube test’ is measure of social dominance that forces an encounter between two unfamiliar animals. The nature of the test apparatus (animals are released simultaneously at opposite ends of a clear, narrow tube that is not big enough for two mice to pass) leads to a subordinate mouse retreating upon meeting a more dominant conspecific. In this task selleck chemicals llc Grb10+/p mutants were found to be significantly less Resminostat likely to back down and retreat than their wild-type (WT) opponents. The initial suggestion for a role of paternal expressed Grb10 in social dominance was found from patterns of whisker barbering that, anecdotally, was thought to be increased in cages containing at least one Grb10+/p mutant [22]. A systematic examination of this phenomenon found this to be the case and, moreover, the sole non-barbered mouse within a cage was significantly more likely to be a Grb10+/p mutant ( Figure 2). Social barbering is

considered a robust correlate of social dominance [23], with the non-barbered animal being the most dominant within a group. Taken together with the tube-test, these findings suggest that the normal function of paternal Grb10 is to temper social dominance behaviour. What is particularly interesting about Grb10 is that whilst expression in the CNS is from the paternal copy only, Grb10 expression in other tissues is from the maternal copy only. Parental allele specific expression is also observed for human GRB10 [24], and yet thus far this is the only imprinted gene known to have such complex tissue specific regulation. As well as having allele-specific expression, the two parental alleles of Grb10 also have distinct functions, whereby maternal Grb10 has a no direct effect on behaviour, but is involved in the regulation of foetal growth [25], and influences insulin signalling and fat deposition during adulthood [26].