Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies

Hao Zhu, Samar Shah, Ng Shyh-Chang, Gen Shinoda, William S. Einhorn, Srinivas R. Viswanathan, Ayumu Takeuchi, Corinna Grasemann, John L. Rinn, Mary F. Lopez, Joel N. Hirschhorn, Mark R. Palmert, George Q. Daley

Research output: Contribution to journalArticle

212 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)626-630
Number of pages5
JournalNature genetics
Volume42
Issue number7
DOIs
StatePublished - Jul 1 2010

ASJC Scopus subject areas

  • Genetics

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    Zhu, H., Shah, S., Shyh-Chang, N., Shinoda, G., Einhorn, W. S., Viswanathan, S. R., Takeuchi, A., Grasemann, C., Rinn, J. L., Lopez, M. F., Hirschhorn, J. N., Palmert, M. R., & Daley, G. Q. (2010). Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies. Nature genetics, 42(7), 626-630. https://doi.org/10.1038/ng.593