| First Author | Wethmar K | Year | 2010 |
| Journal | Genes Dev | Volume | 24 |
| Issue | 1 | Pages | 15-20 |
| PubMed ID | 20047998 | Mgi Jnum | J:155795 |
| Mgi Id | MGI:4415737 | Doi | 10.1101/gad.557910 |
| Citation | Wethmar K, et al. (2010) C/EBPbetaDeltauORF mice--a genetic model for uORF-mediated translational control in mammals. Genes Dev 24(1):15-20 |
| abstractText | Upstream ORFs (uORFs) are translational control elements found predominantly in transcripts of key regulatory genes. No mammalian genetic model exists to experimentally validate the physiological relevance of uORF-regulated translation initiation. We report that mice deficient for the CCAAT/enhancer-binding protein beta (C/EBPbeta) uORF initiation codon fail to initiate translation of the autoantagonistic LIP (liver inhibitory protein) C/EBPbeta isoform. C/EBPbeta(DeltauORF) mice show hyperactivation of acute-phase response genes, persistent repression of E2F-regulated genes, delayed and blunted S-phase entry of hepatocytes after partial hepatectomy, and impaired osteoclast differentiation. These data and the widespread prevalence of uORFs in mammalian transcriptomes suggest a comprehensive role of uORF-regulated translation in (patho)physiology. |
