| First Author | Puri S | Year | 2013 |
| Journal | Genes Dev | Volume | 27 |
| Issue | 23 | Pages | 2563-75 |
| PubMed ID | 24298056 | Mgi Jnum | J:205272 |
| Mgi Id | MGI:5544509 | Doi | 10.1101/gad.227785.113 |
| Citation | Puri S, et al. (2013) VHL-mediated disruption of Sox9 activity compromises beta-cell identity and results in diabetes mellitus. Genes Dev 27(23):2563-75 |
| abstractText | Precise functioning of the pancreatic beta cell is paramount to whole-body glucose homeostasis, and beta-cell dysfunction contributes significantly to diabetes mellitus. Using transgenic mouse models, we demonstrate that deletion of the von Hippel-Lindau (Vhlh) gene (encoding an E3 ubiquitin ligase implicated in, among other functions, oxygen sensing in pancreatic beta cells) is deleterious to canonical beta-cell gene expression. This triggers erroneous expression of factors normally active in progenitor cells, including effectors of the Notch, Wnt, and Hedgehog signaling cascades. Significantly, an up-regulation of the transcription factor Sox9, normally excluded from functional beta cells, occurs upon deletion of Vhlh. Sox9 plays important roles during pancreas development but does not have a described role in the adult beta cell. beta-Cell-specific ectopic expression of Sox9 results in diabetes mellitus from similar perturbations in beta-cell identity. These findings reveal that assaults on the beta cell that impact the differentiation state of the cell have clear implications toward our understanding of diabetes mellitus. |
