Development of Craniofacial Biomineralization in Mice with Osteogenesis Imperfecta (OI)

Osteogenesis Imperfecta (OI) is a rare autosomal dominant disorder characterized by genetic mutations that affect type I collagen (Col1) synthesis. The severe OI type III phenotype generally includes a short stature, low bone mineral density (BMD), dental problems, hearing loss, and blue sclerae. In this study, we use a mouse model of OI type III to examine how mutations in type I collagen synthesis impact craniofacial biomineralization during postnatal growth. The homozygous recessive osteogenesis imperfecta murine (OIM) is characterized by increased skeletal fractures, low postcranial BMD, progressive skeletal deformities, and small body size. Wild type mice (WT) and OIM littermates (n>3/genotype) were micro-CT scanned at weaning (4 weeks) and adulthood (16 weeks). BMD at three regions of interest (ROI) within the mouse skull was measured using Bruker CTAnalyzer software: (1) the temporomandibular joint (TMJ), (2) the parietal bone (1mm from the sagittal suture), and (3) the anterior maxilla at the incisal alveolus. Mann-Whitney U-tests (?=0.05) were used to compare BMD values between the genotypes for each ROI. At weaning, OIM mice had significantly lower BMD values (g.cm-3 CaHA) than their wild type littermates at all three ROIs, and these differences persist into adulthood. This decrease in BMD reflects decreased deposition of CaHA due to an abnormal collagen framework in the craniofacial skeleton of OIM mice. Ongoing efforts will expand this analysis to quantify the development of BMD at additional regions within the craniofacial skeleton.