Osteogenesis imperfecta (OI) is a disorder of type I collagen characterized by abnormal bone formation and weakened bone architecture. Human patients with OI have larger cranial vaults (macrocephaly), altered cranial base morphology including basilar invagination and platybasia (skull base flattening), and midfacial underdevelopment. The neurocranial changes may affect both underlying nervous tissue and growth patterns of the facial skeleton. However, we still do not fully understand how and when these divergent morphologies occur. The aims of this study are: (1) to investigate the integrated development of the skull and the brain in a mouse model of OI; and (2) to identify the developmental trajectories of these structures to facilitate future therapeutic interventions. We hypothesize that compared to unaffected mice, mice with OI will have decreased brain volumes due to an overall reduction in cranial size and decreased cranial base angles (CBA) due to platybasia. To test these hypotheses, we used the osteogenesis imperfecta murine (OIM or B6C3FE a/a-Col1a2oim /J), a model for the severe type III OI in humans, and unaffected wild-type (WT) littermates. Mice were imaged using in vivo micro-computed tomography (micro-CT) at the juvenile (week 4; 10 OIM/14 WT) and adult (week 16; 9 OIM/11 WT) stages. All measurements were taken in 3D Slicer software. 82 cranial landmarks were used to calculate centroid size, an estimate of overall head size. The segmentations tool was used to create virtual endocasts as a proxy for brain volume. The angle tool was used to measure CBA in the midsagittal plane using three landmarks: foramen cecum, midsphenoidal synchondrosis, and basion. Mann-Whitney U tests were used to compare centroid sizes, brain volumes, and CBA between the genotypes. Both juvenile (p=0.008) and adult (p=0.003) OIM mice were found to have absolutely smaller brains than WT mice. However, OIM mice also have significantly smaller cranial centroid sizes compared to WT mice (p=0.003, p<0.001). When scaled to cranial size, juvenile mice had relatively larger brain volumes (p=0.016) but adult OIM relative brain volumes were not significantly different from WT. No significant difference was seen in CBA at the juvenile (p=0.065) or adult (p=0.171) stages, however a trend was observed for decreased CBA at the adult stage. These results suggest that neurocranial dysmorphologies in OI may be more severe at earlier stages of postnatal development. Previous analyses of these mice have documented relative skeletal macrocephaly in both juvenile and adults, however here we document an increase in relative endocranial volume only at the juvenile stage. A reduction in CBA during growth, possibly due to platybasia, may underlie this decoupling between external and internal cranial morphology. Future work will investigate the effect of CBA on facial growth and midfacial underdevelopment in these mice. A better understanding of the integration and growth trajectory of the neurocranium is foundational for formulating treatments to manage basicranial instabilities in patients with OI.