Craniofacial and Dental Defects in the Col1a1^Jrt/+ Mouse Model of Osteogenesis Imperfecta

Abstract

Certain mutations in the COL1A1 and COL1A2 genes produce clinical symptoms of both osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) that include abnormal craniofacial growth, dental malocclusion, and dentinogenesis imperfecta. A mouse model (Col1a1(Jrt)/+) was recently developed that had a skeletal phenotype and other features consistent with moderate-to-severe OI and also with EDS. The craniofacial phenotype of 4- and 20-wk-old Col1a1(Jrt)/+ mice and wild-type littermates was assessed by micro-computed tomography (µCT) and morphometry. Teeth and the periodontal ligament compartment were analyzed by µCT, light microscopy/histomorphometry, and electron microscopy. Over time, at 20 wk, Col1a1(Jrt)/+ mice developed smaller heads, a shortened anterior cranial base, class III occlusion, and a mandibular side shift with shorter morphology in the masticatory region (maxilla and mandible). Col1a1(Jrt)/+ mice also had changes in the periodontal compartment and abnormalities in the dentin matrix and mineralization. These findings validate Col1a1(Jrt)/+ mice as a model for OI and EDS in humans.

Genotype and malocclusion in patients with osteogenesis imperfecta

“…These pilot results also suggest a role of COL1A2 mutations in bone apposition in maxillary sutures, leading to lack of downward and forward development of the maxilla, and a lateral open bite. This might be in line with previous experimental study in mice with a COL1A 1Jrt/+ mutation showing that age could affect the dimensions of the maxilla . Maxillas were shorter with smaller intermolar distance in mice at the age of 20 weeks compared to mice at the age of 4 weeks.…”

“…However, in a previous study, the type of alpha chain mutated did not result in any differences in skeletal deformities when comparing lumber supine densitometry or histomorphometric outcomes . Although the exact aetiology is still unknown, it seems that mutation in COL1A1 affects mainly long bones as a result of its influence on endochondral ossification . Therefore, cranial bones seem to be less affected by a COL1A1 mutation.…”

Matrix Gla protein deficiency impairs nasal septum growth, causing midface hypoplasia

“…Cephalometric analyses of micro-CT scans of whole heads were done following the method reported by Eimar et al (52). Cephalometric analysis of the basicranium was done according to the modified method reported by Laurita et al (28).…”

Research of distribution pattern of allelic genes and genotypes of C/A polymorphism of COL1A1_1 collagen gene (RS1107946) in children with nasal obstruction of allergic genesis and orthodontic pathology

“…Also, the clinical symptoms of Ehlers-Danlos syndrome and imperfect osteogenesis syndrome, which include abnormal craniofacial growth, abnormal bite of teeth and imperfection of dentinogenesis, cause certain mutations in the COL1A1 and COL1A2 genes [16]. In Sweden, when studying the patterns of distribution of the genotypes of polymorphisms of the COL1A1 and COL1A2 genes in 223 people with imperfect osteogenesis, it was revealed that N-ended spiral mutations in both α1 and α2 chains were associated with the lack of dentinogenesis imperfection [17].…”