Uncoupling of growth plate maturation and bone formation in mice lacking both Schnurri-2 and Schnurri-3
Open accessAbstract
Formation and remodeling of the skeleton relies on precise temporal and spatial regulation of genes expressed in cartilage and bone cells. Debilitating diseases of the skeletal system occur when mutations arise that disrupt these intricate genetic regulatory programs. Here, we report that mice bearing parallel null mutations in the adapter proteins Schnurri2 (Shn2) and Schnurri3 (Shn3) exhibit defects in patterning of the axial skeleton during embryogenesis. Postnatally, these compound mutant mice develop a unique osteochondrodysplasia. The deletion of Shn2 and Shn3 impairs growth plate maturation during endochondral ossification but simultaneously results in massively elevated trabecular bone formation. Hence, growth plate maturation and bone formation can be uncoupled under certain circumstances. These unexpected findings demonstrate that both unique and redundant functions reside in the Schnurri protein family that are required for proper skeletal patterning and remodeling.
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- Authors
- Jones, D. C., Schweitzer, M. N., Wein, M., Sigrist, K., Takagi, T., Ishii, S., & Glimcher, L. H.
- Affiliations
- Harvard University (US)
- RIKEN (JP)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-04-19
- Volume
- 107
- Issue
- 18
- Pages
- 8254-8258
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2889532
- OpenAlex
- W2127745370
- Cited by
- 21
- References
- 28
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 1 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 4
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K99AR055668)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD055601, HD055601)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Keywords
- adaptor proteins, endochondral ossification, trabecular bone formation, skeletal dysplasia, skeletal development, skeletal remodeling, compound mutant mice, gene redundancy
- MeSH terms
- Animals, DNA-Binding Proteins, Growth Plate, Osteochondrodysplasias, Osteogenesis, Phenotype, Bone Density, Mice, Knockout, Gene Expression Regulation, Developmental, Gene Dosage, Mice
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