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

被引：1322

作者：

Ventura, Andrea ^{[1
]}

Young, Amanda G. ^{[1
]}

Winslow, Monte M. ^{[1
]}

Lintault, Laura ^{[1
]}

Meissner, Alex ^{[2
]}

Erkeland, Stefan J. ^{[3
]}

Newman, Jamie ^{[1
]}

Bronson, Roderick T. ^{[4
]}

Crowley, Denise ^{[1
]}

Stone, James R. ^{[5
]}

Jaenisch, Rudolf ^{[2
]}

Sharp, Phillip A. ^{[1
]}

Jacks, Tyler ^{[1
,6
]}

机构：

[1] MIT, Ctr Canc Res, Cambridge, MA 02139 USA

[2] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA

[3] Erasmus Univ, Med Ctr, Dept Hematol, NL-3015 GE Rotterdam, Netherlands

[4] Tufts Univ, Sch Vet, Dept Biomed Sci, North Grafton, MA USA

[5] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA

[6] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA

来源：

CELL | 2008年 / 132卷 / 05期

关键词：

D O I：

10.1016/j.cell.2008.02.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

miR-17 similar to 92, miR-106b similar to 25, and miR-106a similar to 363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of miR-17 similar to 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 miR17 similar to 92 die shortly after birth with lung hypoplasia and a ventricular septal defect. The miR-17 similar to 92 cluster is also essential for B cell development. Absence of miR-17 similar to 92 leads to increased levels of the proapoptotic protein Bim and inhibits B cell development at the pro-Bto pre-B transition. Furthermore, while ablation of miR-106b similar to 25 or miR-106a similar to 363 has no obvious phenotypic consequences, compound mutant embryos lacking both miR-106b similar to 25 and miR-17 similar to 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 similar to 92 and its functions during B lymphopoiesis and lung development.

引用

页码：875 / 886

页数：12

共 52 条

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