Characterization of craniofacial morphology in a conditional dicer mutant mouse

Recent studies have shown that small non‐coding RNAs, including small interfering RNAs (siRNAs) and highly conserved microRNAs (miRNAs), are actively involved in the regulation of gene expression at multiple levels including chromatin architecture, transcription, RNA editing, RNA stability, and translation. Biogenesis of functional siRNAs and miRNAs from double‐stranded RNA precursors requires the action of Dicer, an RNase III family member. Mutations in the Dicer allele have been shown to cause several developmental defects in plants and animals and more recently has been linked to several different types of human diseases, including cancers and HIV. In the mouse, mutation of Dicer leads to early embryonic lethality. In order to examine the role of Dicer and small RNAs in craniofacial morphogenesis, a tissue‐specific conditional Dicer knockout mouse was generated. Mutant mice live to only embryonic day (E) 17.5, but exhibit marked craniofacial dimorphisms. A comparison of mutant mice to wild type (WT) liter mates reveals gross morphological defects in the craniofacial region. Phenotypic features of mutant embryos at E17.5 included agenesis of the frontal bones, midface retrognathia, and apparent disruption in palatogenesis. These preliminary results suggest a prominent role for Dicer and small RNAs in craniofacial development. Financial Support: This work was supported by a faculty development grant (SMS Rocha‐Sanchez) from HFF * Correspondent author