Osteogenesis imperfecta (OI) is a heritable connective tissue disorder affecting the synthesis and structure of type I collagen (Col1) due to autosomal dominant mutations in proa1(I) or proa2(I) collagen genes (COL1A1 and COL1A2). Clinical manifestations of the severe OI type III include bone fragility, reduced physical stature, low bone mineral density, and midface hypoplasia resulting in a “triangle face” phenotype. To investigate the influence of Col1 on juvenile craniofacial morphology, we used the homozygous OI murine (OIM ) mouse model at the weaning stage (21 days).

The OIM mouse has a nonlethal recessively inherited mutation of the COL1A2 gene and exhibits adult cranial and post-cranial phenotypes similar to humans with severe OI type III. OIM and wild type (WT) littermates were weaned at 21 days and scanned in-vivo with a Skyscan 1176 micro-CT system. Craniofacial landmarks were collected using 3D Slicer software. Interlandmark distances (ILDs) and centroid sizes were calculated using Past 2.17 software. ILDS were scaled against skull/mandible centroid size to account for the effect of overall body size on shape analyses. Mann-Whitney U-tests were used to compare both absolute and relative (scaled) ILDs between the genotypes.

Craniomandibular centroid sizes and absolute linear distances (skull, rostrum, palate, and mandible lengths) demonstrate that the OIM mice are smaller overall than their WT littermates. When scaled to centroid size, juvenile OIM mice have a decrease in nasal length, midface height, and mandibular diastema length and an increase in hemimandible length compared to WT mice. For a given skull length, OIM mice have shorter faces in both the anteroposterior and dorsoventral dimensions.

The morphometric changes seen in the juvenile OIM mice replicate the “triangle face” that is commonly seen in human pediatric populations with OI. This suggests that this mouse model can potentially be used to investigate the structural changes underlying the human OI phenotype and potential therapeutic interventions. The results of this study can be used to inform future studies of craniofacial developmental in older OIM mice.