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Effect of immunosuppressants on a mouse model of osteogenesis imperfecta type V harboring a heterozygous Ifitm5 c.-14C > T mutation
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| Title: | Effect of immunosuppressants on a mouse model of osteogenesis imperfecta type V harboring a heterozygous Ifitm5 c.-14C > T mutation |
| Authors: | Hanagata, Nobutaka Browse this author | | Takemura, Taro Browse this author | | Kamimura, Keiko Browse this author | | Koda, Toshiaki Browse this author →KAKEN DB |
| Issue Date: | 3-Dec-2020 |
| Publisher: | Nature Research |
| Journal Title: | Scientific reports |
| Volume: | 10 |
| Issue: | 1 |
| Start Page: | 21197 |
| Publisher DOI: | 10.1038/s41598-020-78403-1 |
| Abstract: | Osteogenesis imperfecta (OI) type V is an autosomal dominant disorder caused by the c.-14C >T mutation in the interferon-induced transmembrane protein 5 gene (IFITM5), however, its onset mechanism remains unclear. In this study, heterozygous c.-14C >T mutant mice were developed to investigate the effect of immunosuppressants (FK506 and rapamycin) on OI type V. Among the mosaic mice generated by Crispr/Cas9-based technology, mice with less than 40% mosaic ratio of c.-14C > T mutation survived, whereas those with more than 48% mosaic ratio exhibited lethal skeletal abnormalities with one exception. All heterozygous mutants obtained by mating mosaic mice with wild-type mice exhibited a perinatal lethal phenotype due to severe skeletal abnormalities. Administration of FK506, a calcineurin inhibitor, in the heterozygous fetuses improved bone mineral content (BMC) of the neonates, although it did not save the neonates from the lethal effects of the mutation, whereas rapamycin, an mTOR inhibitor, reduced BMC, suggesting that mTOR signaling is involved in the bone mineralization of heterozygous mutants. These findings could clarify certain aspects of the onset mechanism of OI type V and enable development of therapeutics for this condition. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/80680 |
| Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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