The Craniofacial Phenotype in a Mouse Model of Osteogenesis Imperfecta

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2018-03-15

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Menegaz, Rachel A.
Ladd, Summer

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Abstract

Purpose: Osteogenesis Imperfecta (OI, or “brittle bone disease”) is a rare disorder that is caused by genetic point mutations (COL1A1/COL1A2) that affect type 1 collagen. In OI type III (severe) patients, limb bones are more susceptible to skeletal fractures and the bones of the craniofacial region are underdeveloped. Some OI type III patients also suffer from dental malocclusions or fractures (dentinogenesis imperfecta). The goal of this project is to describe the facial phenotype in an OI mouse model, to see if this model can be used to test potential behavioral and pharmaceutical interventions. Methods: The homozygous OI murine (OIM-/-), a mouse strain with a nonlethal recessively inherited mutation of the COL1A2 gene, is a potential model for the human OI type III. OIM-/- and wild type (WT) littermates were raised from weaning (21 days) to adulthood (16 weeks). Digital 3D craniofacial landmarks were taken from in-vivo micro CT scans, and Kuskal-Wallis ANOVAs (α=0.05) were used to compare centroid size and interlandmark distances between genotypes. Results: Adult OIM-/- mice were found to have decreased cranial and mandibular centroid sizes, compared to WT mice. OIM-/- mice also show several morphological similarities to the OI type III human phenotype, such as shortened basicrania, facial hypoplasia, and altered dental spacing. Conclusions: We conclude that this mouse model shows potential for future investigations of the growth mechanisms underlying the craniofacial presentation of OI. Subsequently, we will next explore the possibility of using increased masticatory loading during the early growth period to stimulate craniofacial bone growth and improve bone quality in the OIM mouse model.

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