Ablation of the FACIT collagen XII disturbs musculoskeletal ECM organization and causes patella dislocation and myopathy
Zhu, M.; Metzen, F.; Betz, J.; Hopkinson, M.; Pitsillides, A. A.; Paulsson, M.; Koch, M.; Brachvogel, B.; Izu, Y.; Schreiber, G.; Imhof, T.; Birk, D. E.; Heilig, J.; Niehoff, A.; Altmueller, J.
Show abstract
Collagen XII, belonging to the fibril-associated collagens with interrupted triple helix (FACIT) family, assembles from three identical -chains encoded by the COL12A1 gene. The trimeric molecule consists of three N-terminal noncollagenous NC3 domains joined by disulfide bonds followed by a short interrupted collagen triple helix at the C-terminus. Collagen XII is expressed widely in the musculoskeletal system and mutations in the COL12A1 gene cause an Ehlers-Danlos/myopathy overlap syndrome, which is associated with skeletal abnormalities and muscle weakness. Our study defines the role of collagen XII in patella development using the Col12a1-/- mouse model. Deficiency in Col12a1 expression causes malformed facies patellaris femoris grooves at an early stage, which leads to patella subluxation and growth retardation. Due to the patella subluxation, more muscle fibers with centralized nuclei occur in the quadriceps than in the gastrocnemius muscles indicating a local effect. To further understand the role of collagen XII in the skeletal tissues single cell RNAseq (scRNA-seq) was performed. Comparison of the gene expression in the tenocyte cell sub-population of wild type and Col12a1-/- mice showed that several matrix genes are altered. Finally, we reinvestigated collagen XII deficient patients and observed a patella instability.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Functional analysis of cell lines derived from SMAD3-related Loeys-Dietz Syndrome patients provides insights into genotype-phenotype relations 94%
- DOCK3 is a dosage-sensitive regulator of skeletal muscle and Duchenne muscular dystrophy-associated pathologies. 94%
- Loss of adenylosuccinate synthetase 1 in mice recapitulates features of ADSS1 myopathy 93%
Similar papers in this journal
- Specific Deletion of Axin1 Leads to Activation of β-Catenin/BMP Signaling Resulting in Fibular Hemimelia Phenotype in Mice 96%
- Dynamic regulation of inter-organelle communication by ubiquitylation controls skeletal muscle development and disease onset 95%
- Tenotomy-induced muscle atrophy is sex-specific and independent of NFκB 94%
Similar papers in this journal
- Rcn3 is Involved in Postnatal Tendon Development by Regulating Collagen Modification and Fibrillogenesis 96%
- Altered TGFB1 regulated pathways promote accelerated tendon healing in the superhealer MRL/MpJ mouse 95%
- Dysregulation of cell migration by matrix metalloproteinases in geleophysic dysplasia 93%