Dnm3os, a Non-Coding RNA, Is Required for Normal Growth and Skeletal Development in Mice

被引:122
作者
Watanabe, Tokumitsu [1 ,2 ]
Sato, Takahiro [2 ]
Amano, Tomokazu [2 ]
Kawamura, Yumiko [2 ]
Kawamura, Naohiro [3 ]
Kawaguchi, Hiroshi [3 ]
Yamashita, Naohide [1 ]
Kurihara, Hiroki [2 ]
Nakaoka, Takashi [1 ]
机构
[1] Univ Tokyo, Inst Med Sci, Dept Adv Med Sci, Tokyo 1088639, Japan
[2] Univ Tokyo, Grad Sch Med, Div Biochem & Mol Biol, Dept Physiol Chem & Metab, Tokyo, Japan
[3] Univ Tokyo, Fac Med, Dept Orthopaed Surg, Tokyo 1138654, Japan
关键词
non-coding RNA; micro RNA; skeletal development;
D O I
10.1002/dvdy.21787
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
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.
引用
收藏
页码:3738 / 3748
页数:11
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