Targeted Deletion Reveals Essential and Overlapping Functions of the miR-1792 Family of miRNA Clusters
- 作者：Andrea Ventura ; Am ; a G. Young ; Monte M. Winslow ; Laura Lintault ; Alex Meissner ; Stefan J. Erkel ; Jamie Newman ; Roderick T. Bronson ; Denise Crowley ; James R. Stone ; Rudolf Jaenisch ; Phillip A. Sharp
- 关键词：Wave scattering ; Many-body scattering ; Condensed matter physics
- 刊名：Cell
- 出版年：2008
- 期刊代码：50_00928674
- 类别：med
- 出版时间：7 March 2008
- 卷：132
- 期：5
- 页码：875-886
- 文件大小：1785 K
摘要
miR-17
border="0">92, miR-106bborder="0">25, and miR-106aborder="0">363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of miR-17border="0">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-17border="0">92 die shortly after birth with lung hypoplasia and a ventricular septal defect. The miR-17border="0">92 cluster is also essential for B cell development. Absence of miR-17border="0">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-106bborder="0">25 or miR-106aborder="0">363 has no obvious phenotypic consequences, compound mutant embryos lacking both miR-106bborder="0">25 and miR-17border="0">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-17border="0">92 and its functions during B lymphopoiesis and lung development.
border="0">92, miR-106bborder="0">25, and miR-106aborder="0">363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of miR-17border="0">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-17border="0">92 die shortly after birth with lung hypoplasia and a ventricular septal defect. The miR-17border="0">92 cluster is also essential for B cell development. Absence of miR-17border="0">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-106bborder="0">25 or miR-106aborder="0">363 has no obvious phenotypic consequences, compound mutant embryos lacking both miR-106bborder="0">25 and miR-17border="0">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-17border="0">92 and its functions during B lymphopoiesis and lung development.