biostudies-literatureDu SWNEI NIH HHSNICHD NIH HHSNIAID NIH HHSCanadian Government | Natural Sciences and Engineering Research Council of Canada (NSERC)NHGRI NIH HHSResearch to Prevent Blindness (RPB)Knights Templar Eye Foundation (KTEF)NIGMS NIH HHSHHS | NIH (NIH)HHMI (HHMI)e2506257122https://www.ebi.ac.uk/biostudies/studies/S-EPMC12415246biostudies-literatureUnknown122(35)In vivo genome editing has the potential to address many inherited and environmental disorders. However, a major hurdle for the clinical translation of genome editing is safe, efficient delivery to disease-relevant tissues. A modality-agnostic reporter animal model that facilitates rapid, precise, and quantifiable assessment of functional delivery and editing could greatly enhance the evaluation and translation of delivery technologies. Here, we present the development of the tdTomato in vivo genome-editing reporter (TIGER) mouse, a reporter strain that harbors an integrated and constitutively expressed mutated tdTomato gene in the <i>Polr2a</i> locus. The mutations (Q115X, Q357X) abolish fluorescence, but successful adenine base editing (ABE) or prime editing (PE) restores tdTomato fluoreProceedings of the National Academy of Sciences of the United States of AmericaTIGER: A tdTomato in vivo genome-editing reporter mouse for investigating precision-editor delivery approaches.PMC12415246P30EY034070N/AR01EY036994R35GM118062UG3 AI150551Career-Starter Research GrantsRM1HG009490R01 HD101642R01 EY034501R01 EY026177RM1 HG009490U01 AI142756R01HD101642R01EY034501UG3AI150551P30 EY034070R35 GM118062T32GM008620F30EY033642R01 EY036994T32 GM008620U01AI142756F30 EY033642UnrestrictedR01EY026177HHMIDu SWLauterborn JCZode GPalczewski KDong ZChen PZHolubowicz RYan ALHa SKaipa BRGall CMPalczewska GLiu DRfalseTIGER: A tdTomato in vivo genome-editing reporter mouse for investigating precision-editor delivery approaches.In vivo genome editing has the potential to address many inherited and environmental disorders. However, a major hurdle for the clinical translation of genome editing is safe, efficient delivery to disease-relevant tissues. A modality-agnostic reporter animal model that facilitates rapid, precise, and quantifiable assessment of functional delivery and editing could greatly enhance the evaluation and translation of delivery technologies. Here, we present the development of the tdTomato in vivo genome-editing reporter (TIGER) mouse, a reporter strain that harbors an integrated and constitutively expressed mutated tdTomato gene in the <i>Polr2a</i> locus. The mutations (Q115X, Q357X) abolish fluorescence, but successful adenine base editing (ABE) or prime editing (PE) restores tdTomato fluore2025-01-01T00:00:00Z2025 Sep2026-06-02T02:25:21.77Z2026-04-13T03:11:45.118ZS-EPMC124152464088053410.1073/pnas.2506257122