| Item type |
文献 / Documents(1) |
| 公開日 |
2024-09-26 |
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| item_1722929371688 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1093/jbmrpl/ziae050 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1093/jbmrpl/ziae050 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Loss-of-function OGFRL1 variants identified in autosomal recessive cherubism families |
|
言語 |
en |
| 著者 |
Kittaka, Mizuho
Mizuno, Noriyoshi
森野, 豊之
Yoshimoto, Tetsuya
Zhu, Tianli
Liu, Sheng
Wang, Ziyi
Mayahara, Kotoe
Iio, Kyohei
Kondo, Kaori
Kondo, Toshio
Hayashi, Tatsuhide
Coghlan, Sarah
Teno, Yayoi
Doan, Andrew Anh Phung
Levitan, Marcus
Choi, Roy B
Matsuda, Shinji
Ouhara, Kazuhisa
Wan, Jun
Cassidy, Annelise M.
Pelletier, Stephane
Nampoothiri, Sheela
Urtizberea, Andoni J.
Robling, Alexander G.
Ono, Mitsuaki
Kawakami, Hideshi
Reichenberger, Ernst J.
Ueki, Yasuyoshi
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Cherubism (OMIM 118400) is a rare craniofacial disorder in children characterized by destructive jawbone expansion due to the growth of inflammatory fibrous lesions. Our previous studies have shown that gain-of-function mutations in SH3 domain-binding protein 2 (SH3BP2) are responsible for cherubism and that a knock-in mouse model for cherubism recapitulates the features of cherubism, such as increased osteoclast formation and jawbone destruction. To date, SH3BP2 is the only gene identified to be responsible for cherubism. Since not all patients clinically diagnosed with cherubism had mutations in SH3BP2, we hypothesized that there may be novel cherubism genes and that these genes may play a role in jawbone homeostasis. Here, using whole exome sequencing, we identified homozygous loss-of-function variants in the opioid growth factor receptor like 1 (OGFRL1) gene in 2 independent autosomal recessive cherubism families from Syria and India. The newly identified pathogenic homozygous variants were not reported in any variant databases, suggesting that OGFRL1 is a novel gene responsible for cherubism. Single cell analysis of mouse jawbone tissue revealed that Ogfrl1 is highly expressed in myeloid lineage cells. We generated OGFRL1 knockout mice and mice carrying the Syrian frameshift mutation to understand the in vivo role of OGFRL1. However, neither mouse model recapitulated human cherubism or the phenotypes exhibited by SH3BP2 cherubism mice under physiological and periodontitis conditions. Unlike bone marrow-derived M-CSF-dependent macrophages (BMMs) carrying the SH3BP2 cherubism mutation, BMMs lacking OGFRL1 or carrying the Syrian mutation showed no difference in TNF-ɑ mRNA induction by LPS or TNF-ɑ compared to WT BMMs. Osteoclast formation induced by RANKL was also comparable. These results suggest that the loss-of-function effects of OGFRL1 in humans differ from those in mice and highlight the fact that mice are not always an ideal model for studying rare craniofacial bone disorders. |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
rare disease |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
cherubism |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
autosomal recessive |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
whole exome sequencing |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
OGFRL1 |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
mutation |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
loss of function |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
mouse model |
| bibliographic_information |
en : JBMR Plus
巻 8,
号 6,
p. ziae050,
発行日 2024-04-09
|
| 収録物ID |
|
|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
24734039 |
| 出版者 |
|
|
出版者 |
Oxford University Press |
|
言語 |
en |
| 出版者 |
|
|
出版者 |
American Society for Bone and Mineral Research |
|
言語 |
en |
| item_10001_rights_15 |
|
|
言語 |
en |
|
権利情報 |
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
| item_1723180141928 |
|
|
識別子 |
408231 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
jbmrp_8_6_ziae050.pdf (1.9 MB)
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