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A new mouse line for cell ablation by diphtheria toxin subunit A controlled by a Cre‐dependent FLEx switch

Recombinase responsive mouse lines expressing diphtheria toxin subunit A (DTA) are well established tools for targeted ablation of genetically defined cell populations. Here we describe a new knock‐in allele at the Gt(Rosa)26Sor locus that retains the best features of previously described DTA alleles—including a CAG promoter, attenuated mutant DTA cDNA, and ubiquitous EGFP labeling—with the addition of a Cre‐dependent FLEx switch for tight control of expression. The FLEx switch consists of two pairs of antiparallel lox sites requiring Cre‐mediated recombination for inversion of the DTA to the proper orientation for transcription. We demonstrate its utility by Cre‐dependent ablation of both a broad domain in the embryonic nervous system and a discrete population of cells in the fetal gonads. We conclude that this new DTA line is useful for targeted ablation of genetically‐defined cell populations.