| First Author | Zhu H | Year | 2010 |
| Journal | Nat Genet | Volume | 42 |
| Issue | 7 | Pages | 626-30 |
| PubMed ID | 20512147 | Mgi Jnum | J:166568 |
| Mgi Id | MGI:4848022 | Doi | 10.1038/ng.593 |
| Citation | Zhu H, et al. (2010) Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies. Nat Genet 42(7):626-30 |
| abstractText | Recently, genome-wide association studies have implicated the human LIN28B locus in regulating height and the timing of menarche. LIN28B and its homolog LIN28A are functionally redundant RNA-binding proteins that block biogenesis of let-7 microRNAs. lin-28 and let-7 were discovered in Caenorhabditis elegans as heterochronic regulators of larval and vulval development but have recently been implicated in cancer, stem cell aging and pluripotency. The let-7 targets Myc, Kras, Igf2bp1 and Hmga2 are known regulators of mammalian body size and metabolism. To explore the function of the Lin28-Let-7 pathway in vivo, we engineered transgenic mice to express Lin28a and observed in them increased body size, crown-rump length and delayed onset of puberty. Investigation of metabolic and endocrine mechanisms of overgrowth in these transgenic mice revealed increased glucose metabolism and insulin sensitivity. Here we report a mouse that models the human phenotypes associated with genetic variation in the Lin28-Let-7 pathway. |
