Dnm3os, a non-coding RNA, is required for normal growth and skeletal development in mice.
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.
Watanabe
Tokumitsu
T
Department of Advanced Medical Science, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Sato
Takahiro
T
Amano
Tomokazu
T
Kawamura
Yumiko
Y
Kawamura
Naohiro
N
Kawaguchi
Hiroshi
H
Yamashita
Naohide
N
Kurihara
Hiroki
H
Nakaoka
Takashi
T
D000818:Animals; D001835:Body Weight; D001846:Bone Development; D001842:Bone and Bones / Q000196:embryology* / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter / Q000235:genetics; D005838:Genotype; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D022661:RNA, Untranslated / Q000235:genetics*
D022661:RNA, Untranslated