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

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.
Authors	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
Journal	Nature genetics (Nat Genet) Vol. 42 Issue 7 Pg. 626-30 (Jul 2010) ISSN: 1546-1718 [Electronic] United States
PMID	20512147 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Blood Glucose Insulin Lin-28 protein, mouse MicroRNAs RNA-Binding Proteins mirnlet7 microRNA, mouse Glucose
Topics	Animals Blood Glucose (metabolism) Body Size (genetics, physiology) Female Gene Expression Profiling Genetic Association Studies Glucose (metabolism) Humans Insulin (blood) Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic MicroRNAs (genetics, metabolism) Models, Animal Oligonucleotide Array Sequence Analysis Phenotype RNA-Binding Proteins (genetics, metabolism) Reverse Transcriptase Polymerase Chain Reaction Sexual Maturation (genetics, physiology) Time Factors

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