Department of Pediatric Dentistry, Peking University and School and Hospital of Stomatology, Beijing, China.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Dev Dyn. 2020 Jul;249(7):884-897. doi: 10.1002/dvdy.166. Epub 2020 Mar 12.
Inactivating mutations in the gene for cartilage-associated protein (CRTAP) cause osteogenesis imperfecta type VII in humans, with a phenotype that can include craniofacial defects. Dental and craniofacial manifestations have not been a focus of case reports to date. We analyzed the craniofacial and dental phenotype of Crtap mice by skull measurements, micro-computed tomography (micro-CT), histology, and immunohistochemistry.
Crtap mice exhibited a brachycephalic skull shape with fusion of the nasofrontal suture and facial bones, resulting in mid-face retrusion and a class III dental malocclusion. Loss of CRTAP also resulted in decreased dentin volume and decreased cellular cementum volume, though acellular cementum thickness was increased. Periodontal dysfunction was revealed by decreased alveolar bone volume and mineral density, increased periodontal ligament (PDL) space, ectopic calcification within the PDL, bone-tooth ankylosis, altered immunostaining of extracellular matrix proteins in bone and PDL, increased pSMAD5, and more numerous osteoclasts on alveolar bone surfaces.
Crtap mice serve as a useful model of the dental and craniofacial abnormalities seen in individuals with osteogenesis imperfecta type VII.
软骨相关蛋白（CRTAP）基因失活突变导致人类发生 VII 型成骨不全症，其表型可包括颅面缺陷。迄今为止，牙和颅面表现并不是病例报告的重点。我们通过颅骨测量、微计算机断层扫描（micro-CT）、组织学和免疫组织化学分析了 Crtap 小鼠的颅面和牙表型。
Crtap 小鼠表现出短头畸形的颅骨形状，伴有鼻额缝和面部骨骼融合，导致中面部后缩和 III 类错牙合。CRTAP 的缺失还导致牙本质体积减少和细胞性牙骨质体积减少，尽管无细胞牙骨质厚度增加。牙周功能障碍表现为牙槽骨体积和矿密度减少、牙周韧带（PDL）空间增加、PDL 内异位钙化、骨牙粘连、骨和 PDL 中细胞外基质蛋白免疫染色改变、pSMAD5 增加以及牙槽骨表面的破骨细胞增多。
Crtap 小鼠可作为 VII 型成骨不全症患者牙和颅面异常的有用模型。
