Effect of Marrow-localized Growth Hormone Gene Therapy in a Mouse Model Ofosteogenesis Imperfecta

نویسنده

  • D. and McEwen
چکیده

Introduction. Based on clinical trials on limited numbers of human volunteers, recombinant human growth hormone injections are presently offered to children who are moderately to severely affected by osteogenesis imperfecta (O.I.), with the dual objectives of stimulating osteogenic activity and increasing ultimate body height. We previously demonstrated that low-level expression of a growth hormone transgene in developing erythroid cells in the marrow of mice enhanced bone growth and deposition without other major systemic effects (1). When the transgene was bred into and expressed by heterozygous oim mice, a model for mild O.I., the biomechanical performance of their femurs was normalized in 4-point bending (2). This improvement was attributed to anabolic changes in the deposition of bone matrix, because the causative genetic mutation in their a2 type I collagen gene was not addressed by this approach. The objective of the present experiment was to determine whether the marrow-based growth hormone delivery strategy could be adapted to a gene therapy for O.I.

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تاریخ انتشار 2002