Neurocranial growth in the OIM mouse model of osteogenesis imperfecta.

Abstract

Osteogenesis imperfecta (OI) is a disorder of type I collagen characterized by abnormal bone formation. The OI craniofacial phenotype includes midfacial underdevelopment, as well as neurocranial changes (e.g., macrocephaly and platybasia) that may also affect underlying nervous tissues. This study aims to better understand how OI affects the integrated development of the neurocranium and the brain. Juvenile and adult mice with OI (OIM) and unaffected wild type (WT) littermates were imaged using in vivo micro-computed tomography (microCT). Virtual endocast models were used to measure brain volume, and 3D landmarks were collected from the cranium and brain endocasts. Geometric morphometric analyses were used to compare brain shape and integration between the genotypes. OIM mice had increased brain volumes (relative to cranial centroid size) only at the juvenile stage. No significant difference was seen in cranial base angle (CBA) between OIM and WT mice. However, CBA was higher in juvenile than in adult OIM mice. Brain shape was significantly different between OIM and WT mice at both stages, with OIM mice having more globular brains than WT mice. Neurocranial and brain morphology were strongly integrated within both genotypes, while adult OIM mice tended to have lower levels of skull-brain integration than WT mice. These results suggest that neurocranial dysmorphologies in OI may be more severe at earlier stages of postnatal development. Decreased skull-brain integration in adult mice suggests that compensatory mechanisms may exist during postnatal growth to maintain neurological function despite significant changes in neurocranial morphology.