Mouse fracture models: a primer

Mouse fracture models have become increasingly versatile tools for the study of how fractures heal. Mouse genes can be specifically modified using transgenic technology, thereby providing the opportunity to study the roles of individual genes during the fracture healing process. The mouse rib fracture model is a reliable model for use in studies of gene expression during fracture healing, which do not involve fixation or biomechanical testing. The versatility of the mouse femur fracture model is based on the fact that femoral anatomy makes femur fractures more easily fixed and reproducible than other mouse fracture models. To investigate the mechanism of normal fracture healing, a mouse femur or tibia is usually fractured using a 3-point bending device and is then closely fixed with special devices. To investigate issues involving delayed healing and non-union formation, the mouse femur is often osteotomized and then openly fixed using different devices as needed. The newest generation of 3-point bending devices allow for generation of reproducible transverse femur fractures in mice of different ages and sizes. Methods to assess fracture healing range from conventional radiological, histological and biomechanical analyses to MRI, micro-CT, radioisotope imaging, and specific molecular and genetic assays. Live gait analysis can also be performed if needed. Overall, current mouse fracture models provide a large array of validated and standardized protocols to analyze physiological, biomechanical, histological, molecular, and genetic aspects of normal and pathological fracture healing. The present review summarizes some of the most common techniques and their applications.