Introduction: Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a new form of Ehlers-Danlos syndrome that is primarily caused by a systemic deficiency of dermatan sulfate stemming from CHST14 or DSE mutations. In recent years, significant advancements have been made in the creation of Chst14 gene-deleted (Chst14-/-) mice as mcEDS models aimed at studying this particular disease. However, the precise pathogenic mechanisms of spinal deformity are not fully understood. This study investigated the mechanisms of spinal deformity by radiological and pathological evaluation of a mouse model of mcEDS.
Methods: Twenty-eight 1-year-old mice (Chst14-/-: 12 mice, Chst14+/+: 16 mice) were analyzed. For radiological analysis, all animals were examined for spinal deformities by CT imaging. For pathological examination, the structures of the vertebrae and intervertebral discs were stained for histological evaluation. We also measured the area ratio of the bone trabeculae in vertebral bodies.
Results: Thoracolumbar kyphosis on CT was detected in 6 (50.0%) Chst14-/- mice and 2 (12.5%) Chst14+/+ mice, which was a significant difference (p=0.0441). Disc changes were significantly more frequent in Chst14-/- mice (7 [58.3%] vs. 3 [18.8%], p=0.0497), whilevertebral crest to vertebral body ratio was significantly smaller (24.6 ± 5.8 % vs. 30.6 ± 6.5 %, p=0.0478).
Conclusions: Dermatan sulfate may play an important role in the maintenance of spinal alignment. Our findings indicate that abnormalities of the intervertebral discs and bone trabeculae are involved in the pathogenesis of spinal deformity in mcEDS.