The present invention is based, at least in part, on the generation of cells, cell lines and non-human mammals that contain a synthetic conditional allele of the Dicer1 gene. Many of the constructs, methods, animals and cells of the invention feature recombinase recognition sites (in certain embodiments, loxP sites) positioned on either flank of a sequence that comprises exons 14, 15 and 16 of the Dicer1 gene (in certain embodiments, the mouse Dicer1 gene). Through readily manipulable introduction, administration, or expression of a recombinase (in certain aspects of the invention, the Cre recombinase of bacteriophage P1), exons 14 through 16 of Dicer1 may be directedly excised, producing a functional knockout of Dicer1 in cells containing these recombinase-induced alleles of the invention.