Decreased chondrocyte proliferation and dysregulated apoptosis in the cartilage growth plate are key features of a murine model of epiphyseal dysplasia caused by a matn3 mutation
| Autor: | Raimund Wagener, Matthew Leighton, Michael D. Briggs, Tobias Starborg, Roger S. Meadows, Farhana Suleman, Lynnette Knowles, David J. Thornton, Karl E. Kadler, Seema Nundlall, Raymond P. Boot-Handford |
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| Rok vydání: | 2007 |
| Předmět: |
Dwarfism
Apoptosis Mice Transgenic Cartilage metabolism Biology Endoplasmic Reticulum Osteochondrodysplasias Article Chondrocyte Multiple epiphyseal dysplasia Mice Chondrocytes Genetics medicine Animals Matrilin Proteins Molecular Biology Endochondral ossification Genetics (clinical) Cell Proliferation Bone growth Extracellular Matrix Proteins Models Genetic Cartilage General Medicine medicine.disease Cell biology Disease Models Animal medicine.anatomical_structure Dysplasia Mutation Immunology Molecular Chaperones |
| Zdroj: | Human Molecular Genetics. 16:1728-1741 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | Disruption to endochondral ossification leads to delayed and irregular bone formation and can result in a heterogeneous group of genetic disorders known as the chondrodysplasias. One such disorder, multiple epiphyseal dysplasia (MED), is characterized by mild dwarfism and early-onset osteoarthritis and can result from mutations in the gene encoding matrilin-3 (MATN3). To determine the disease mechanisms that underpin the pathophysiology of MED we generated a murine model of epiphyseal dysplasia by knocking-in a matn3 mutation. Mice that are homozygous for the mutation develop a progressive dysplasia and have short-limbed dwarfism that is consistent in severity with the relevant human phenotype. Mutant matrilin-3 is retained within the rough endoplasmic reticulum of chondrocytes and is associated with an unfolded protein response. Eventually, there is reduced proliferation and spatially dysregulated apoptosis of chondrocytes in the cartilage growth plate, which is likely to be the cause of disrupted linear bone growth and the resulting short-limbed dwarfism in the mutant mice. |
| Databáze: | OpenAIRE |
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