摘要：SummaryTheEscherichia colidihydrofolate reductase (DHFR) destabilizing domain (DD) serves as a promising approach to conditionally regulate protein abundance in a variety of tissues. To test whether this approach could be effectively applied to a wide variety of aged and disease-related ocular mouse models, we evaluated the DHFR DD system in the eyes of aged mice (up to 24 months), a light-induced retinal degeneration (LIRD) model, and two genetic models of retinal degeneration (rd2andAbca4−/−mice). The DHFR DD was effectively degraded in all model systems, includingrd2mice, which showed significant defects in chymotrypsin proteasomal activity. Moreover, trimethoprim (TMP) administration stabilized the DHFR DD in all mouse models. Thus, the DHFR DD-based approach allows for control of protein abundance in a variety of mouse models, laying the foundation to use this strategy for the conditional control of gene therapies to potentially treat multiple eye diseases.Graphical abstractDisplay OmittedHighlights•Destabilizing domains (DDs) confer conditional control of ocular protein abundance•The DHFR DD is effectively turned over and stabilized in aged mouse’s retina•DHFR DDs perform well in environmental and genetic retinal degenerative modelsMedicine; Therapeutics; Molecular biology; Cell biology;
