The maternally-expressed miR-379/miR-410 cluster is positioned at the imprinted Dlk1-Dio3 domain. It consists of 39 placental-mammal specific miRNA genes. In order to unravel its physiological roles in an unbiased manner, we generated a constitutive Knock-Out (KO) mouse model in which the entire cluster (~60 kb) was removed through Cre-LoxP-mediated site-specific recombination. We found that a fraction of heterozygote neonates (30-40 %) with a maternal, but not paternal, deletion die shortly after birth (within 24-48 hours), very likely due to defects in maintaining a perinatal source of energy within safe range. We are now investigating the physiological roles of the miR-379/miR-410 cluster in surviving adult KO mice, notably its involvement in neurobiology and behavior processes.