Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies
Copyright policy )Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies
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.
- Boston Children's Hospital United States
- Brigham and Women's Faulkner Hospital United States
- University of Toronto Canada
- Harvard Stem Cell Institute, Cambridge, MA, USA United States
- Dana-Farber Cancer Institute United States
Blood Glucose, Male, Mice, Inbred BALB C, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Medizin, RNA-Binding Proteins, Mice, Transgenic, Article, Mice, Inbred C57BL, Mice, MicroRNAs, Glucose, Phenotype, Models, Animal, Animals, Body Size, Humans, Insulin, Female, Genetic Association Studies, Oligonucleotide Array Sequence Analysis
Blood Glucose, Male, Mice, Inbred BALB C, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Medizin, RNA-Binding Proteins, Mice, Transgenic, Article, Mice, Inbred C57BL, Mice, MicroRNAs, Glucose, Phenotype, Models, Animal, Animals, Body Size, Humans, Insulin, Female, Genetic Association Studies, Oligonucleotide Array Sequence Analysis
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