Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters

Andrea Ventura; Amanda G. Young; Monte M. Winslow; Laura Lintault; Alex Meissner; Stefan J. Erkeland; Jamie Newman; Roderick T. Bronson; Denise Crowley; James R. Stone; Rudolf Jaenisch; Phillip A. Sharp; Tyler Jacks

doi:10.1016/j.cell.2008.02.019

Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters

Andrea Ventura, Amanda G. Young, Monte M. Winslow, Laura Lintault, Alex Meissner, Stefan J. Erkeland, Jamie Newman, Roderick T. Bronson, Denise Crowley, James R. Stone, Rudolf Jaenisch, Phillip A. Sharp, Tyler Jacks^*

^*Corresponding author for this work

Hematology

Research output: Contribution to journal › Article › Academic › peer-review

1458 Citations (Scopus)

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.

Original language	English
Pages (from-to)	875-886
Number of pages	12
Journal	Cell
Volume	132
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2008.02.019
Publication status	Published - 7 Mar 2008

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@article{f88c059d69fd45c784652a79a4346eaf,

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",

year = "2008",

month = mar,

day = "7",

doi = "10.1016/j.cell.2008.02.019",

language = "English",

volume = "132",

pages = "875--886",

journal = "Cell",

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TY - JOUR

T1 - Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters

AU - Ventura, Andrea

AU - Young, Amanda G.

AU - Winslow, Monte M.

AU - Lintault, Laura

AU - Meissner, Alex

AU - Erkeland, Stefan J.

AU - Newman, Jamie

AU - Bronson, Roderick T.

AU - Crowley, Denise

AU - Stone, James R.

AU - Jaenisch, Rudolf

AU - Sharp, Phillip A.

AU - Jacks, Tyler

PY - 2008/3/7

Y1 - 2008/3/7

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/39749143354

U2 - 10.1016/j.cell.2008.02.019

DO - 10.1016/j.cell.2008.02.019

M3 - Article

C2 - 18329372

AN - SCOPUS:39749143354

SN - 0092-8674

VL - 132

SP - 875

EP - 886

JO - Cell

JF - Cell

IS - 5

ER -

Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters

Abstract

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