Grant: Travel Awards - Institute Community Support

Introduction: Scoliosis can be infantile or juvenile in onset; however, it is more frequently identified in older children, particularly girls as they enter puberty. Untreated scoliosis progresses with age and there are currently few non-operative therapies for severe scoliosis. Furthermore, current animal models inadequately represent human scoliosis: a characteristic necessary in pre-clinical research. We noticed that FGFR3-/- mice, in addition to severe kyphosis and other skeletal abnormalities, develop progressive scoliosis and may be a viable model of scoliosis. Methods: Ninety-six male and female mice of wild-type and Fgfr3-/- backgrounds were X-rayed to measure scoliosis Cobb angles, body mass, and other anatomical dimensions. Mice were euthanized at 4 to 25 weeks old and processed for micro-CT and histological analysis to compare parameters such as vertebral and inter-vertebral disc (IVD) morphology, vertebral rotation, and cellular characterisation. All knockout mice were paired with an age and gender matched wild-type counterpart for micro-CT and histological analysis. Results: Fgfr3-/- mice developed scoliosis by 8 weeks (p<0.05) that progressed until the end of study, reaching a maximum of 40.9±18.3 degrees compared to wild-type counterpart of 5.1±4.2 degrees. Micro-CT analysis of Fgfr3-/- vertebral body micro-architecture revealed decreased bone volume fraction of the convex side, indicating decreased bone quality, and decreased IVD thickness and relative body height on the concave side of the curve. Histological analysis of bone mineralization and cartilage support micro-CT data, and indicates concave IVD compression and convex translation. Conclusion: Because the proposed model features spontaneously occurring scoliosis, we see it as more clinically relevant than surgically induced scoliosis. We propose the Fgfr3-/- mouse as an animal model that is inexpensive, easily available, non-invasive, and closely reproduces the disease.