Pre-weaning craniofacial development in mice with Osteogenesis Imperfecta

dc.creatorMiller, Courtneyen_US
dc.creatorEmmanuel, Tanushaen_US
dc.creatorGonzales, Laurenen_US
dc.creatorHandler, Emmaen_US
dc.creatorOrgan, Jasonen_US
dc.creatorMenegaz, Rachel A.en_US
dc.creator.orcid0000-0003-0748-4290 (Miller, Courtney)
dc.creator.orcid0000-0002-7261-7873 (Menegaz, Rachel)
dc.description.abstractThe craniofacial region plays a pivotal role in various physiological functions, including mastication, speech, and respiration. Early life behaviors have a profound role in shaping adult structure and function. In the early stages of life, all mammals undergo the transition from suckling to mastication, a period coinciding with rapid cranial biomineralization. Osteogenesis imperfecta (OI), a genetic disorder that impacts the production of type I collagen, disrupts biomineralization, leading to craniofacial growth differences affecting overall quality of life. This study investigates the preweaning craniofacial growth trajectory in mice OI (the OIM mouse) compared to unaffected wild type (WT mice). We hypothesize that mice with OI will exhibit smaller overall size and greater craniofacial variation than WT mice due to the abnormal collagen synthesis during skull development. Micro-CT based geometric morphometric analyses of the OIM mouse model (B6C3Fe a/a-Col1a2oim/J) were used to compare craniofacial size and shape differences at birth (P0; n=27 OIM / 20 WT) and postnatal days 7 (P7; n=21/21) and 14 (P14; n=16/20). The SlicerMorph package for 3D Slicer software was used to generate landmark point clouds for the cranium and mandible. Dimension ratios were calculated as width/length for the crania. Principal component analysis with Procrustes ANOVA were used to examine differences between genotypes at each time point, and a canonical variate analysis (CVA) used to identify shape features that maximize the distinction between genotypes across all time points. Results reveal the development of significant differences in both shape and size between the genotypes following birth. At birth, size and shape are similar between genotypes. However, by P7 and P14, OIM mice are significantly (p<0.05) smaller and display pronounced shape changes (p<0.001) characterized by larger neurocranium and shorter viscerocranium. Additionally, OIM mice have significant mandibular alterations by P7 (p<0.001) - shorter ramus, more posterior position of the coronoid, and shorter and wider dental arcade. All of these changes align with the suckling developmental stage, suggesting changes in the ratio of growth between the neurocranium and the viscerocranium during early life. Widening the neurocranium while shortening the viscerocranium during this critical developmental stage alters the masticatory muscle line of action, consequently, influences the health of individuals with OI. These findings underscore the suckling stage’s significance in shaping the foundational structures for later life, providing insights into OI craniofacial development, and suggest potential benefits to directing interventions toward an earlier time point for more effective treatment of OI.en_US
dc.description.sponsorshipNational Science Foundation BA-DDRIG (BCS-2236027), UNTHSC Preclinical Imaging Core Pilot Grant, UNTHSC Department of Physiology & Anatomy SEED Granten_US
dc.titlePre-weaning craniofacial development in mice with Osteogenesis Imperfectaen_US