miR-17
border="0">92, miR-106b
border="0">25, and
miR-106a
border="0">363 belong to a family of highly conserved miRNA clusters. Amplification and overexpression of
miR-17
border="0">92 is o
bserved 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
border="0">92 die shortly after
birth with lung hypoplasia and a ventricular septal defect. The
miR-17
border="0">92 cluster is also essential for B cell development. A
bsence of
miR-17
border="0">92 leads to increased levels of the proapoptotic protein Bim and inhi
bits B cell development at the pro-B to pre-B transition. Furthermore, while a
blation of
miR-106b
border="0">25 or
miR-106a
border="0">363 has no o
bvious phenotypic consequences, compound mutant em
bryos lacking
both
miR-106b
border="0">25 and
miR-17
border="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-17
border="0">92 and its functions during B lymphopoiesis and lung development.