Generation of a multipurpose Prdm16 mouse allele by targeted gene trapping

• Published in: Disease models & mechanisms 2017-07, Vol.10 (7), p.909-922
• Main Authors: Strassman, Alexander, Schnütgen, Frank, Dai, Qi, Jones, Jennifer C, Gomez, Angela C, Pitstick, Lenore, Holton, Nathan E, Moskal, Russell, Leslie, Erin R, von Melchner, Harald, Beier, David R, Bjork, Bryan C
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Brain - metabolism; Breeding; Cleft palate; Cloning; Conditional gene trap; DNA-Binding Proteins - genetics; Embryo, Mammalian - cytology; Embryonic Stem Cells - metabolism; Gene Deletion; Gene expression; Gene Targeting; Genes, Reporter; Genetic Vectors - metabolism; Genomes; Head - embryology; Mandible; Mice; Micrognathia; Mouse Models; Mutation; Mutation - genetics; Organ Specificity; Phenotype; Pierre Robin sequence; Plasmids; Reading; Resource; Transcription Factors - genetics
• ISSN: 1754-8403; 1754-8411; 1754-8411
• DOI: 10.1242/dmm.029561

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.