Generation of a multipurpose Prdm16 mouse allele by targeted gene trapping

Gene trap mutagenesis is a powerful tool to create loss-of-function mutations in mice and other model organisms. Modifications of traditional gene trap cassettes, including addition of conditional features in the form of Flip-excision (FlEx) arrays to enable directional gene trap cassette inversions by Cre and Flpe site-specific recombinases, greatly enhanced their experimental potential. By taking advantage of these conditional gene trap cassettes, we developed a generic strategy for generating conditional mutations and validated this strategy in mice carrying a multipurpose allele of the transcription factor gene. We demonstrate that the gene trap insertion creates a null mutation replicating the Pierre Robin sequence-type cleft palate phenotype of other mutant mice. Consecutive breeding to and deleter mice spatially restricted loss to regions of the forebrain expressing the homeobox gene , demonstrating the utility of the technology for the analysis of tissue-specific gene functions.