Experimental alteration of the microRNA profile of the mouse embryo: heritable phenotypes in the adult

We previously identified a unique genetic feature of Autism Spectrum Disorder (ASD) in human patients and established mouse models, namely the low to very low level of six microRNAs, miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p and miR-499a-5p. We attempted to interfere experimentally with the expression in the mouse of two of them, miR19a-3p and miR499a-5p by microinjecting into the one-cell embryo either the complementary sequence or an excess of the microRNA. Both approaches resulted in low levels in the somatic tissues and sperm of the targeted microRNAs (nascent) and their pri and pre precursors. The altered miRNA profiles were inherited by progenies of crosses with untreated partners together with behavior alterations partly characteristic of ASD patients and animal models. An excess of miRNA in the eggs leads to a specific downregulation, we propose variations of single-stranded miRNA, as effectors of its own transcription in eukaryotes.