論文 - 詳細
| RRC ID | 82425 |
|---|---|
| 著者 | Yamashita M, Ogawa C, Zhang B, Kobayashi T, Nomura A, Barker C, Zou C, Yamanaka S, Hayashi KI, Shinkai Y, Moro K, Fargarasan S, Imami K, Seita J, Shirai F, Sawasaki T, Kanemaki MT, Taniuchi I. |
| タイトル | Cell-type specific, inducible and acute degradation of targeted protein in mice by two degron systems. |
| ジャーナル | Nat Commun |
| Abstract |
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 TIR1F74G (OsTIR1)-auxin-inducible degron 2 (AID2) and human cereblon (hCRBN)-SALL4 degron (S4D). Efficient degradation of Satb1Venus 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. |
| 巻・号 | 15(1) |
| ページ | 10129 |
| 公開日 | 2024-11-29 |
| DOI | 10.1038/s41467-024-54308-9 |
| PII | 10.1038/s41467-024-54308-9 |
| PMID | 39613744 |
| PMC | PMC11607430 |
| MeSH | Animals Degrons Female HEK293 Cells Humans Male Mice Mice, Inbred C57BL Mice, Knockout Oryza / genetics Oryza / metabolism Proteolysis* Repressor Proteins / genetics Repressor Proteins / metabolism Transcription Factors / genetics Transcription Factors / metabolism Tumor Suppressor Proteins |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 46 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) Jurkat(RCB0806) |