The Specificity of Conditional Gene Targeting: A Case for Cre Reporters (Immunity)

Becher et al. (2018) published a timely warning about several critical aspects of conditional gene targeting in mice, including its specificity. As the authors correctly point out, the cell type specificity of gene deletion is often assumed rather than ascertained, which may lead to incorrect conclusions. They make a case against the use of Cre-inducible fluorescent reporters as a surrogate measurement of recombination specificity, instead proposing two solutions: (1) making Cre-expressing alleles as fusions with fluorescent proteins to assess Cre expression specificity and (2) carefully examining the deletion of each targeted gene, ideally at single-cell resolution.