Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters.
Apoptosis-Regulatory-Proteins, B-Lymphocytes, Cell-Survival, Embryonic-Stem-Cells, Fetus, Genes-Lethal, Heart-Septal-Defects-Ventricular, Lung-Diseases, Membrane-Proteins, Mice, MicroRNAs, Multigene-Family, Proto-Oncogene-Proteins, Sequence-Deletion
Cell 2008 Mar; 132(5):875-86.
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.
Ventura, A; Young, A G.; Winslow, M M.; Lintault, L; Meissner, A; Erkeland, S J.; Newman, J; Bronson, R T.; Crowley, D; Stone, J R.; Jaenisch, R; Sharp, P A.; and Jacks, T, "Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters." (2008). Faculty Research 2000 - 2009. 1739.