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PMID: 18329372 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Cell ·Vol. 132 ·No. 5 ·2008-03-07 ·Pages 875-86

Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR, Jaenisch R, Sharp PA, Jacks T

Abstract

miR-17 approximately 92, miR-106b approximately 25, and miR-106a approximately 363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of miR-1792 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 approximately 92 die shortly after birth with lung hypoplasia and a ventricular septal defect. The miR-17 approximately 92 cluster is also essential for B cell development. Absence of miR-17 approximately 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 approximately 25 or miR-106a approximately 363 has no obvious phenotypic consequences, compound mutant embryos lacking both miR-106b approximately 25 and miR-17 approximately 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 approximately 92 and its functions during B lymphopoiesis and lung development.

MeSH Terms
3' Untranslated Regions/metabolism Animals Apoptosis Regulatory Proteins/metabolism B-Lymphocytes/cytology Bcl-2-Like Protein 11 Cell Survival Embryonic Stem Cells/metabolism Fetus/cytology Genes, Lethal Heart Septal Defects, Ventricular/genetics Lung Diseases/genetics Membrane Proteins/metabolism Mice MicroRNAs/genetics,metabolism Multigene Family Proto-Oncogene Proteins/metabolism Sequence Deletion
Chemicals
3' Untranslated Regions Apoptosis Regulatory Proteins BCL2L11 protein, human Bcl-2-Like Protein 11 Bcl2l11 protein, mouse Membrane Proteins MicroRNAs Proto-Oncogene Proteins
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Ventura Andrea
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Young Amanda G
Winslow Monte M
Lintault Laura
Meissner Alex
Erkeland Stefan J
Newman Jamie
Bronson Roderick T
Crowley Denise
Stone James R
Jaenisch Rudolf
Sharp Phillip A
Jacks Tyler
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2008.02.019
Published
2008-03-07
Pages
875-86
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2323338
Subset
IM
Grants
NCI NIH HHS · P30 CA014051-35 · United States
NCI NIH HHS · P01 CA042063-220012 · United States
NCI NIH HHS · P01 CA042063 · United States
NCI NIH HHS · P30 CA014051 · United States
NCI NIH HHS · P01 CA042063-21A10012 · United States
NCI NIH HHS · 2-PO1-CA42063-21 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM034277 · United States
NCI NIH HHS · P30 CA014051-36 · United States
NIGMS NIH HHS · R01-GM34277 · United States
NCI NIH HHS · P30-CA14051 · United States
NCI NIH HHS · P30 CA014051-34 · United States
NIAID NIH HHS · U19 AI056900 · United States
Corrections
CommentIn
PMID: 18490933
External Links
PubMed source DOI: 10.1016/j.cell.2008.02.019 PMC Full Text View journal details
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