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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.

Pubmed ID: 20512147


  • Zhu H
  • Shah S
  • Shyh-Chang N
  • Shinoda G
  • Einhorn WS
  • Viswanathan SR
  • Takeuchi A
  • Grasemann C
  • Rinn JL
  • Lopez MF
  • Hirschhorn JN
  • Palmert MR
  • Daley GQ


Nature genetics

Publication Data

July 28, 2010

Associated Grants

  • Agency: NCI NIH HHS, Id: 5 T32 CA09172-35
  • Agency: NIH HHS, Id: DP1 OD000256
  • Agency: NIH HHS, Id: DP1 OD000256-05
  • Agency: NCI NIH HHS, Id: K08 CA157727
  • Agency: NICHD NIH HHS, Id: R01HD048960
  • Agency: NCI NIH HHS, Id: T32 CA009172
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Blood Glucose
  • Body Size
  • Female
  • Gene Expression Profiling
  • Genetic Association Studies
  • Glucose
  • Humans
  • Insulin
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs
  • Models, Animal
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • RNA-Binding Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sexual Maturation
  • Time Factors