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The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice
BRIL (bone-restricted IFITM-like), is a short transmembrane protein expressed almost exclusively in osteoblasts. Although much is known about its bone-restricted gene expression pattern and protein biochemical and topological features, little information is available for BRIL physiological function....
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589259/ https://www.ncbi.nlm.nih.gov/pubmed/28880886 http://dx.doi.org/10.1371/journal.pone.0184568 |
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author | Patoine, Alexa Husseini, Abdallah Kasaai, Bahar Gaumond, Marie-Hélène Moffatt, Pierre |
author_facet | Patoine, Alexa Husseini, Abdallah Kasaai, Bahar Gaumond, Marie-Hélène Moffatt, Pierre |
author_sort | Patoine, Alexa |
collection | PubMed |
description | BRIL (bone-restricted IFITM-like), is a short transmembrane protein expressed almost exclusively in osteoblasts. Although much is known about its bone-restricted gene expression pattern and protein biochemical and topological features, little information is available for BRIL physiological function. Two autosomal dominant forms of osteogenesis imperfecta (OI) are caused by distinct, but recurrent mutations in the BRIL gene. Yet, the underlying mechanisms by which those mutations lead to OI are still poorly understood. A previous report indicated that BRIL knockout (KO) mice had bone deformities, shortened long bones, and reproductive problems. Here we generated and systematically analyzed the skeletal phenotype of a new global Bril KO/LacZ knockin mouse model. KO mice reproduced and thrived normally up to 12 month of age. The skeletal phenotype of KO and WT littermates was assessed at embryonic (E13.5 to E18.5) and postnatal (2 days, 3 weeks, 3 months and 8 months) time-points. Embryos from E13.5 through to E18.5 showed significant X-Gal staining in all skeletal elements without any apparent patterning anomalies. Although bone deformities were never observed at any postnatal ages, minor and transient differences were noted in terms of bone length and static uCT parameters, but not systematically across all ages and genders. These changes, however, were not accompanied by significant alteration in bone material properties as assessed by a 3-point bending test. In addition, no changes were detected in circulating serum markers of bone turnover (P1NP, CTX-I, and osteocalcin). Gene expression monitoring also revealed no major impact of the loss of BRIL. Further, when mice were challenged with a surgically-induced fracture in tibia, bones repaired equally well in the KO mice as compared to WT. Finally, we showed that BRIL C-terminus is not a bona fide binding site for calcium. In conclusion, our in depth analysis suggest that skeletal patterning, bone mass accrual and remodeling in mice proceeded independent of BRIL. |
format | Online Article Text |
id | pubmed-5589259 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55892592017-09-15 The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice Patoine, Alexa Husseini, Abdallah Kasaai, Bahar Gaumond, Marie-Hélène Moffatt, Pierre PLoS One Research Article BRIL (bone-restricted IFITM-like), is a short transmembrane protein expressed almost exclusively in osteoblasts. Although much is known about its bone-restricted gene expression pattern and protein biochemical and topological features, little information is available for BRIL physiological function. Two autosomal dominant forms of osteogenesis imperfecta (OI) are caused by distinct, but recurrent mutations in the BRIL gene. Yet, the underlying mechanisms by which those mutations lead to OI are still poorly understood. A previous report indicated that BRIL knockout (KO) mice had bone deformities, shortened long bones, and reproductive problems. Here we generated and systematically analyzed the skeletal phenotype of a new global Bril KO/LacZ knockin mouse model. KO mice reproduced and thrived normally up to 12 month of age. The skeletal phenotype of KO and WT littermates was assessed at embryonic (E13.5 to E18.5) and postnatal (2 days, 3 weeks, 3 months and 8 months) time-points. Embryos from E13.5 through to E18.5 showed significant X-Gal staining in all skeletal elements without any apparent patterning anomalies. Although bone deformities were never observed at any postnatal ages, minor and transient differences were noted in terms of bone length and static uCT parameters, but not systematically across all ages and genders. These changes, however, were not accompanied by significant alteration in bone material properties as assessed by a 3-point bending test. In addition, no changes were detected in circulating serum markers of bone turnover (P1NP, CTX-I, and osteocalcin). Gene expression monitoring also revealed no major impact of the loss of BRIL. Further, when mice were challenged with a surgically-induced fracture in tibia, bones repaired equally well in the KO mice as compared to WT. Finally, we showed that BRIL C-terminus is not a bona fide binding site for calcium. In conclusion, our in depth analysis suggest that skeletal patterning, bone mass accrual and remodeling in mice proceeded independent of BRIL. Public Library of Science 2017-09-07 /pmc/articles/PMC5589259/ /pubmed/28880886 http://dx.doi.org/10.1371/journal.pone.0184568 Text en © 2017 Patoine et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Patoine, Alexa Husseini, Abdallah Kasaai, Bahar Gaumond, Marie-Hélène Moffatt, Pierre The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice |
title | The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice |
title_full | The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice |
title_fullStr | The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice |
title_full_unstemmed | The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice |
title_short | The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice |
title_sort | osteogenic cell surface marker bril/ifitm5 is dispensable for bone development and homeostasis in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589259/ https://www.ncbi.nlm.nih.gov/pubmed/28880886 http://dx.doi.org/10.1371/journal.pone.0184568 |
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