@article{fdef318d71964ef29f19d614b0038673,
title = "Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters",
abstract = "miR-17∼92, miR-106b∼25, and miR-106a∼363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of miR-17∼92 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∼92 die shortly after birth with lung hypoplasia and a ventricular septal defect. The miR-17∼92 cluster is also essential for B cell development. Absence of miR-17∼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∼25 or miR-106a∼363 has no obvious phenotypic consequences, compound mutant embryos lacking both miR-106b∼25 and miR-17∼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∼92 and its functions during B lymphopoiesis and lung development.",
author = "Andrea Ventura and Young, \{Amanda G.\} and Winslow, \{Monte M.\} and Laura Lintault and Alex Meissner and Erkeland, \{Stefan J.\} and Jamie Newman and Bronson, \{Roderick T.\} and Denise Crowley and Stone, \{James R.\} and Rudolf Jaenisch and Sharp, \{Phillip A.\} and Tyler Jacks",
note = "Funding Information: This work was supported by grant 2-PO1-CA42063-21 from the National Institutes of Health and in part by Cancer Center Support (core) grant P30-CA14051 from the National Cancer Institute, by United States Public Health Service RO1-GM34277 from the National Institutes of Health, and by an RNA Interference as a Weapon Against Terrorism Grant U19 AI056900 from the National Institutes of Health to PAS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. T.J. is a Howard Hughes Investigator and a Daniel K. Ludwig Scholar. A.V. was supported by a fellowship from the American Italian Cancer Research Foundation. A.G.Y. is recipient of a David Koch Graduate Fellowship. M.M.W. is a Merck Fellow of the Damon Runyon Cancer Research Foundation. S.E. was supported by the Dutch Cancer Society, KWF kankerbestrijding. We thank Mark Schlissel and Alice Shaw for help and discussion, and Sergei Koralov, Stefan Muljo, and Klaus Rajewsky for sharing their results prior to publication. ",
year = "2008",
month = mar,
day = "7",
doi = "10.1016/j.cell.2008.02.019",
language = "English",
volume = "132",
pages = "875--886",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "5",
}