Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters
In: Cell, Jg. 132 (2008-03-01), Heft 5, S. 875-886
Online
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Zugriff:
SummarymiR-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.
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Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters
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Autor/in / Beteiligte Person: | Sharp, Phillip A. ; Meissner, Alexander ; Young, Amanda G. ; Erkeland, Stefan J. ; Bronson, Roderick T. ; Ventura, Andrea ; Lintault, Laura ; Newman, Jamie J. ; Winslow, Monte M. ; Jacks, Tyler ; Stone, James R. ; Jaenisch, Rudolf ; Crowley, Denise |
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Zeitschrift: | Cell, Jg. 132 (2008-03-01), Heft 5, S. 875-886 |
Veröffentlichung: | Elsevier BV, 2008 |
Medientyp: | unknown |
ISSN: | 0092-8674 (print) |
DOI: | 10.1016/j.cell.2008.02.019 |
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