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Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters.

miR-17 approximately 92, miR-106b approximately 25, and miR-106a approximately 363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of miR-1792 is observed in human cancers, and its oncogenic properties have been confirmed in a mouse model of B cell lymphoma. Here we show that mice deficient for miR-17 approximately 92 die shortly after birth with lung hypoplasia and a ventricular septal defect. The miR-17 approximately 92 cluster is also essential for B cell development. Absence of miR-17 approximately 92 leads to increased levels of the proapoptotic protein Bim and inhibits B cell development at the pro-B to pre-B transition. Furthermore, while ablation of miR-106b approximately 25 or miR-106a approximately 363 has no obvious phenotypic consequences, compound mutant embryos lacking both miR-106b approximately 25 and miR-17 approximately 92 die at midgestation. These results provide key insights into the physiologic functions of this family of microRNAs and suggest a link between the oncogenic properties of miR-17 approximately 92 and its functions during B lymphopoiesis and lung development.

Pubmed ID: 18329372


  • Ventura A
  • Young AG
  • Winslow MM
  • Lintault L
  • Meissner A
  • Erkeland SJ
  • Newman J
  • Bronson RT
  • Crowley D
  • Stone JR
  • Jaenisch R
  • Sharp PA
  • Jacks T



Publication Data

March 7, 2008

Associated Grants

  • Agency: NCI NIH HHS, Id: 2-PO1-CA42063-21
  • Agency: NCI NIH HHS, Id: P01 CA042063
  • Agency: NCI NIH HHS, Id: P01 CA042063-21A10012
  • Agency: NCI NIH HHS, Id: P01 CA042063-220012
  • Agency: NCI NIH HHS, Id: P30 CA014051
  • Agency: NCI NIH HHS, Id: P30 CA014051-34
  • Agency: NCI NIH HHS, Id: P30 CA014051-35
  • Agency: NCI NIH HHS, Id: P30 CA014051-36
  • Agency: NCI NIH HHS, Id: P30-CA14051
  • Agency: NIGMS NIH HHS, Id: R01-GM34277
  • Agency: NIAID NIH HHS, Id: U19 AI056900
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • 3' Untranslated Regions
  • Animals
  • Apoptosis Regulatory Proteins
  • B-Lymphocytes
  • Cell Survival
  • Embryonic Stem Cells
  • Fetus
  • Genes, Lethal
  • Heart Septal Defects, Ventricular
  • Lung Diseases
  • Membrane Proteins
  • Mice
  • MicroRNAs
  • Multigene Family
  • Proto-Oncogene Proteins
  • Sequence Deletion