Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of genetic skeletal diseases.
Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are skeletal disorders resulting from mutations in COMP, matrilin-3 or collagen IX and are characterised by short-limbed dwarfism and premature osteoarthritis. Interestingly, recent reports suggest patients can also manifest with m...
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
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| author | Katarzyna A Piróg Yoshihisa Katakura Aleksandr Mironov Michael D Briggs |
| author_facet | Katarzyna A Piróg Yoshihisa Katakura Aleksandr Mironov Michael D Briggs |
| author_sort | Katarzyna A Piróg |
| collection | DOAJ |
| description | Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are skeletal disorders resulting from mutations in COMP, matrilin-3 or collagen IX and are characterised by short-limbed dwarfism and premature osteoarthritis. Interestingly, recent reports suggest patients can also manifest with muscle weakness. Here we present a detailed analysis of two mouse models of the PSACH/MED disease spectrum; ΔD469 T3-COMP (PSACH) and V194D matrilin-3 (MED). In grip test experiments T3-COMP mice were weaker than wild-type littermates, whereas V194D mice behaved as controls, confirming that short-limbed dwarfism alone does not contribute to PSACH/MED-related muscle weakness. Muscles from T3-COMP mice showed an increase in centronuclear fibers at the myotendinous junction. T3-COMP tendons became more lax in cyclic testing and showed thicker collagen fibers when compared with wild-type tissue; matrilin-3 mutant tissues were indistinguishable from controls. This comprehensive study of the myopathy associated with PSACH/MED mutations enables a better understanding of the disease progression, confirms that it is genotype specific and that the limb weakness originates from muscle and tendon pathology rather than short-limbed dwarfism itself. Since some patients are primarily diagnosed with neuromuscular symptoms, this study will facilitate better awareness of the differential diagnoses that might be associated with the PSACH/MED spectrum and subsequent care of PSACH/MED patients. |
| format | Article |
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| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
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| spelling | doaj-art-c7bab605078c429bb10a25c44f8d6f282025-08-20T02:22:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8241210.1371/journal.pone.0082412Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of genetic skeletal diseases.Katarzyna A PirógYoshihisa KatakuraAleksandr MironovMichael D BriggsPseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are skeletal disorders resulting from mutations in COMP, matrilin-3 or collagen IX and are characterised by short-limbed dwarfism and premature osteoarthritis. Interestingly, recent reports suggest patients can also manifest with muscle weakness. Here we present a detailed analysis of two mouse models of the PSACH/MED disease spectrum; ΔD469 T3-COMP (PSACH) and V194D matrilin-3 (MED). In grip test experiments T3-COMP mice were weaker than wild-type littermates, whereas V194D mice behaved as controls, confirming that short-limbed dwarfism alone does not contribute to PSACH/MED-related muscle weakness. Muscles from T3-COMP mice showed an increase in centronuclear fibers at the myotendinous junction. T3-COMP tendons became more lax in cyclic testing and showed thicker collagen fibers when compared with wild-type tissue; matrilin-3 mutant tissues were indistinguishable from controls. This comprehensive study of the myopathy associated with PSACH/MED mutations enables a better understanding of the disease progression, confirms that it is genotype specific and that the limb weakness originates from muscle and tendon pathology rather than short-limbed dwarfism itself. Since some patients are primarily diagnosed with neuromuscular symptoms, this study will facilitate better awareness of the differential diagnoses that might be associated with the PSACH/MED spectrum and subsequent care of PSACH/MED patients.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0082412&type=printable |
| spellingShingle | Katarzyna A Piróg Yoshihisa Katakura Aleksandr Mironov Michael D Briggs Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of genetic skeletal diseases. PLoS ONE |
| title | Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of genetic skeletal diseases. |
| title_full | Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of genetic skeletal diseases. |
| title_fullStr | Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of genetic skeletal diseases. |
| title_full_unstemmed | Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of genetic skeletal diseases. |
| title_short | Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of genetic skeletal diseases. |
| title_sort | mild myopathy is associated with comp but not matn3 mutations in mouse models of genetic skeletal diseases |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0082412&type=printable |
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