Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557;Department of Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China; and.
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557;
Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):E2851-7. doi: 10.1073/pnas.1407777111. Epub 2014 Jun 30.
Ablation of a single miRNA gene rarely leads to a discernable developmental phenotype in mice, in some cases because of compensatory effects by other functionally related miRNAs. Here, we report that simultaneous inactivation of two functionally related miRNA clusters (miR-34b/c and miR-449) encoding five miRNAs (miR-34b, miR-34c, miR-449a, miR-449b, and miR-449c) led to sexually dimorphic, partial perinatal lethality, growth retardation, and infertility. These developmental defects correlated with the dysregulation of ∼ 240 target genes, which are mainly involved in three major cellular functions, including cell-fate control, brain development and microtubule dynamics. Our data demonstrate an essential role of a miRNA family in brain development, motile ciliogenesis, and spermatogenesis.
在小鼠中，单个 miRNA 基因的缺失很少导致明显的发育表型，在某些情况下是因为其他功能相关的 miRNA 产生了补偿作用。在这里，我们报告说，两个功能相关的 miRNA 簇（miR-34b/c 和 miR-449）的同时失活，编码五个 miRNA（miR-34b、miR-34c、miR-449a、miR-449b 和 miR-449c）导致了性别二态性、部分围产期致死、生长迟缓和不育。这些发育缺陷与约 240 个靶基因的失调相关，这些靶基因主要涉及三个主要的细胞功能，包括细胞命运控制、大脑发育和微管动力学。我们的数据表明 miRNA 家族在大脑发育、运动纤毛发生和精子发生中具有重要作用。
