Mineral changes in a transgenic mouse model for osteogenesis imperfecta.

A line of transgenic mice has been investigated that expressed moderate levels of an internally deleted human gene for the pro alpha 1(I) chain of type I procollagen to determine if they would make a good model for osteogenesis imperfecta (brittle bone disease). Previous workers have reported extensive fracturing in these mice, with femurs that were shorter and bone that had decreased ash weight, mineral and collagen content. These workers demonstrated increased brittleness in the bone by biomechanical measurements. The molar calcium to phosphorus ratio in bone from patients with osteogenesis imperfecta has previously been reported to be lower than that in normal human bone. Mineral changes were observed at the ultrastructural level in these mice and were comparable with those seen in patients with osteogenesis imperfecta. Bone from both transgenic and normal littermate mice was examined to determine if any similarity with the data for human osteogenesis imperfecta could be drawn. X-ray microanalysis of bone mineral demonstrated a lower calcium to phosphorus molar ratio in transgenic mouse bone than in normal littermates. Fourier-transform infra-red spectroscopy confirmed that the mineral present was apatitic in nature despite the lower calcium to phosphorus molar ratio. Multiple fracture calluses were present on the ribs and on the long bones of the transgenic mice; this was absent in normal littermates. This mouse model may lead to a better understanding of the underlying pathology resulting in fragile bones in osteogenesis imperfecta.