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

Autor: Kemppainen AV; ECM-Hypoxia Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, 90014, Oulu, Finland., Finnilä MA; Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland., Heikkinen A; ECM-Hypoxia Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, 90014, Oulu, Finland., Härönen H; ECM-Hypoxia Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, 90014, Oulu, Finland., Izzi V; ECM-Hypoxia Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, 90014, Oulu, Finland.; Faculty of Medicine, University of Oulu, 90014, Oulu, Finland.; Foundation for the Finnish Cancer Institute, Tukholmankatu 8, 00130, Helsinki, Finland., Kauppinen S; Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland., Saarakkala S; Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.; Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland., Pihlajaniemi T; ECM-Hypoxia Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, 90014, Oulu, Finland., Koivunen J; ECM-Hypoxia Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, 90014, Oulu, Finland. jarkko.koivunen@oulu.fi.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Apr 07; Vol. 12 (1), pp. 5866. Date of Electronic Publication: 2022 Apr 07.
DOI: 10.1038/s41598-022-09653-4
Abstrakt: 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 Col13a1 tm/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 Col13a1 tm/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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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