Dnm3os, a Non-Coding RNA, Is Required for Normal Growth and Skeletal Development in Mice
Dnm3os, a Non-Coding RNA, Is Required for Normal Growth and Skeletal Development in Mice
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DOI：
10.1002/dvdy.21787
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发表时间：
2008-12-01
影响因子：
2.5
通讯作者：
Nakaoka, Takashi
中科院分区：
文献类型：
--
作者：
Watanabe, Tokumitsu;Sato, Takahiro;Nakaoka, Takashi
Dnm 3 os是一种转录成非编码RNA（ncRNA）的基因，包含三种微小RNA（miRNAs），miR-199 a、miR-199 a * 和miR-214，其功能在哺乳动物中尚不清楚。在这项研究中，我们将lacZ基因导入Dnm 3 os位点，以重现其表达模式并破坏其功能。Dnm 3 os（+/lacZ）杂合子胚胎具有β-半乳糖苷酶活性，反映了Dnm 3 os RNA的真实表达模式。大多数Dnm 3 os（lacZ/lacZ）纯合子幼仔在出生后一个月内死亡。出生后，Dnm 3 os（lacZ/lacZ）小鼠表现出几种骨骼异常，包括颅面发育不全，背侧神经弓和脊椎棘突的缺陷，以及骨质减少。重要的是，miR-199 a、miR-199 a * 和miR-214的表达在Dnm 3 os（lacZ/lacZ）胚胎中显著下调，支持Dnm 3 os作为这三种miRNA的前体的假设。因此，Dnm 3 os已经成为一种编码miRNA的基因，它对哺乳动物的正常骨骼发育和身体生长是必不可少的。发展动力学237：3738-3748，2008年。(c)2008 Wiley-Liss，Inc.
Dnm3os, a gene that is transcribed into a non-coding RNA (ncRNA), contains three micro RNAs (miRNAs), miR-199a, miR-199a*, and miR-214, whose functions remain unknown in mammals. In this study, we introduced the lacZ gene into the Dnm3os locus to recapitulate its expression pattern and disrupt its function. Dnm3os(+/lacZ) heterozygous embryos showed beta-galactosidase activity, which reflected the authentic expression pattern of Dnm3os RNA. Most of the Dnm3os(lacZ/lacZ) homozygous pups died within one month of birth. After birth, Dnm3os(lacZ/lacZ) mice exhibited several skeletal abnormalities, including craniofacial hypoplasia, defects in dorsal neural arches and spinous processes of the vertebrae, and osteopenia. Importantly, the expression of miR-199a, miR-199a*, and miR-214 was significantly down-regulated in Dnm3os(lacZ/lacZ) embryos, supporting the assumption that Dnm3os serves as a precursor of these three miRNAs. Thus, Dnm3os has emerged as an miRNA-encoding gene that is indispensable for normal skeletal development and body growth in mammals. Developmental Dynamics 237:3738-3748, 2008. (c) 2008 Wiley-Liss, Inc.