上海交通大学医学院，上海市生殖医学重点实验室的徐晨教授和内华达大学的Wei Yan是这篇文章的通讯作者。

绝大多数单个miRNA基因的敲除，不会对小鼠发育产生明显的影响。这是因为功能相关的miRNA之间存在着某种补偿效应。

研究人员在小鼠模型中同时失活了两个功能重叠的miRNA基因簇，miR-34b/c和miR-449。他们发现，这一措施导致了两性异形（sexually dimorphic）、部分围产期死亡、生长迟缓和不育。

研究显示，这两个基因簇编码了五个miRNA，即miR-34b、miR-34c、miR-449a、miR-449b和miR-449c。而这些miRNA负责调控大约240个目标基因，主要涉及三个关键的细胞功能——细胞命运决定、大脑发育和微管动力学。

当miR-34b/c和miR-449同时失活时，上述基因出现调控异常，进而引起了多种发育缺陷，包括基底前脑结构发育不良、气管和输卵管缺乏运动纤毛，精子生成严重受损等等。

Two miRNA clusters, miR-34b/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis

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.

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