Hermann, MarioMarioHermannStillhard, PatrickPatrickStillhardWildner, HendrikHendrikWildnerSeruggia, DavideDavideSeruggiaKapp, ViktorViktorKappSánchez-Iranzo, HéctorHéctorSánchez-IranzoMercader Huber, Nadia IsabelNadia IsabelMercader Huber0000-0002-0905-6399Montoliu, LluísLluísMontoliuZeilhofer, Hanns UlrichHanns UlrichZeilhoferPelczar, PawelPawelPelczar2024-10-242024-10-242014-04https://boris-portal.unibe.ch/handle/20.500.12422/140303Conditional mutagenesis using Cre recombinase expressed from tissue specific promoters facilitates analyses of gene function and cell lineage tracing. Here, we describe two novel dual-promoter-driven conditional mutagenesis systems designed for greater accuracy and optimal efficiency of recombination. Co-Driver employs a recombinase cascade of Dre and Dre-respondent Cre, which processes loxP-flanked alleles only when both recombinases are expressed in a predetermined temporal sequence. This unique property makes Co-Driver ideal for sequential lineage tracing studies aimed at unraveling the relationships between cellular precursors and mature cell types. Co-InCre was designed for highly efficient intersectional conditional transgenesis. It relies on highly active trans-splicing inteins and promoters with simultaneous transcriptional activity to reconstitute Cre recombinase from two inactive precursor fragments. By generating native Cre, Co-InCre attains recombination rates that exceed all other binary SSR systems evaluated in this study. Both Co-Driver and Co-InCre significantly extend the utility of existing Cre-responsive alleles.en600 - Technology::610 - Medicine & healtharticle10.7892/boris.796162441356110.1093/nar/gkt1361