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

Cell | Mar 7, 2008

http://www.ncbi.nlm.nih.gov/pubmed/18329372

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 RIS Download

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

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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:

Mouse Genome Informatics (Data, Gene Annotation)

GO (Data, Gene Annotation)

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