| First Author | Yamashita M | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 10129 |
| PubMed ID | 39613744 | Mgi Jnum | J:359290 |
| Mgi Id | MGI:7786041 | Doi | 10.1038/s41467-024-54308-9 |
| Citation | Yamashita M, et al. (2024) Cell-type specific, inducible and acute degradation of targeted protein in mice by two degron systems. Nat Commun 15(1):10129 |
| abstractText | Despite its broad application in in vitro studies, the application of targeted protein degradation (TPD) to animal models faces considerable challenges. Here, we develop inducible and cell-type specific TPD systems in mice using two degron systems: Oryza sativa TIR1(F74G) (OsTIR1)-auxin-inducible degron 2 (AID2) and human cereblon (hCRBN)-SALL4 degron (S4D). Efficient degradation of Satb1(Venus) protein by these systems recapitulates phenotypes observed in the Satb1-deficient mice. These TPD are successfully applied in both the fetal and neonatal stages. The OsTIR1-AID2 system proves to be effective for membrane proteins such as PD-1, emulating the effects of the anti-PD-1 antibody. Degradation of Bcl11b reveals a role of Bcl11b which was not characterized by the Cre-loxP system. Collectively, in vivo TPD technologies developed in this study enable inducible, temporal, and cell type-specific depletion of target proteins with high efficacy in mice. These technologies have a wide range of applications in the diverse fields of biological and medical research. |
