University of Oulu

Kemppainen, A.V., Finnilä, M.A., Heikkinen, A. et al. The CMS19 disease model specifies a pivotal role for collagen XIII in bone homeostasis. Sci Rep 12, 5866 (2022).

The CMS19 disease model specifies a pivotal role for collagen XIII in bone homeostasis

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Author: Kemppainen, A. V.1; Finnilä, M. A.2; Heikkinen, A.1;
Organizations: 1ECM-Hypoxia Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, 90014, Oulu, Finland
2Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland
3Faculty of Medicine, University of Oulu, 90014, Oulu, Finland
4Foundation for the Finnish Cancer Institute, Tukholmankatu 8, 00130, Helsinki, Finland
5Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.4 MB)
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Language: English
Published: Springer Nature, 2022
Publish Date: 2022-10-25


Mutations in the COL13A1 gene result in congenital myasthenic syndrome type 19 (CMS19), a disease of neuromuscular synapses and including various skeletal manifestations, particularly facial dysmorphisms. The phenotypic consequences in Col13a1 null mice (Col13a1−/−) recapitulate the muscle findings of the CMS19 patients. Collagen XIII (ColXIII) is exists as two forms, a transmembrane protein and a soluble molecule. While the Col13a1−/− mice have poorly formed neuromuscular junctions, the prevention of shedding of the ColXIII ectodomain in the Col13a1tm/tm mice results in acetylcholine receptor clusters of increased size and complexity. In view of the bone abnormalities in CMS19, we here studied the tubular and calvarial bone morphology of the Col13a1−/− mice. We discovered several craniofacial malformations, albeit less pronounced ones than in the human disease, and a reduction of cortical bone mass in aged mice. In the Col13a1tm/tm mice, where ColXIII is synthesized but the ectodomain shedding is prevented due to a mutation in a protease recognition sequence, the cortical bone mass decreased as well with age and the cephalometric analyses revealed significant craniofacial abnormalities but no clear phenotypical pattern. To conclude, our data indicates an intrinsic role for ColXIII, particularly the soluble form, in the upkeep of bone with aging and suggests the possibility of previously undiscovered bone pathologies in patients with CMS19.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 12
Article number: 5866
DOI: 10.1038/s41598-022-09653-4
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
3111 Biomedicine
Funding: We greatly appreciate professors G. Karsenty and J. Tuukkanen for helpful advice. This work was carried out with the support of The Oulu Laboratory Animal Centre Research Infrastructure, University of Oulu, Finland. Part of the work was carried out with the support of Biocenter Oulu, Transgenic and Tissue Phenotyping Core Facility, supported by the University of Oulu and Biocenter Finland, University of Oulu, Finland. This work was supported by European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 336267, grants from Biocenter Oulu, the Sigrid Jusélius Foundation, The Finnish Medical Association, and the Academy of Finland (grants no. 268378, 273571, 294617 and 284605). Part of research infrastructure has been supported by the European Commission Regional Development Fund (decision nr. 538/2010).
EU Grant Number: (336267) 3D-OA-HISTO - Development of 3D Histopathological Grading of Osteoarthritis
Academy of Finland Grant Number: 268378
Detailed Information: 268378 (Academy of Finland Funding decision)
273571 (Academy of Finland Funding decision)
294617 (Academy of Finland Funding decision)
284605 (Academy of Finland Funding decision)
Dataset Reference: The online version contains supplementary material available at
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