Study Design. Genetic engineering techniques were used to develop an animal model of juvenile scoliosis during a postnatal skeletal-growth stage.
Objective. To investigate the effect of targeted SHP2 (Src homology-2) deficiency in chondrocytes on the development of scoliosis during a juvenile growth stage in mice.
Summary of Background Data. Juvenile idiopathic scoliosis can lead to progressive severe spinal deformity. The pathophysiology and molecular mechanisms responsible for the deformity are unknown. Here, we investigated the role of SHP2 deficiency in chondrocytes as a potential cause of juvenile scoliosis.
Methods. Genetically engineered mice with inducible deletion of SHP2 in chondrocytes were generated. The SHP2 function in chondrocytes was inactivated during a juvenile growth stage from the mouse age of 4 weeks. Radiographical, micro-computed tomographic, and histological assessments were used to analyze spinal changes.
Results. When SHP2 deficiency was induced during the juvenile stage, a progressive kyphoscoliotic deformity (thoracic lordosis and thoracolumbar kyphoscoliosis) developed within 2 weeks of the initiation of SHP2 deficiency. The 3-dimensional micro-computed tomography analysis confirmed the kyphoscoliotic deformity with a rotational deformity of the spine and osteophyte formation. The histological analysis revealed disorganization of the vertebral growth plate cartilage. Interestingly, when SHP2 was disrupted during the adolescent to adult stages, no spinal deformity developed.
Conclusion. SHP2 plays an important role in normal spine development during skeletal maturation. Chondrocyte-specific deletion of SHP2 at a juvenile stage produced a kyphoscoliotic deformity. This new mouse model will be useful for future investigations of the role of SHP2 deficiency in chondrocytes as a mechanism leading to the development of juvenile scoliosis.
Level of Evidence: N/A
Currently, a genetic animal model of scoliosis is unavailable. We developed severe scoliosis in mice by inducing Src homology-2 deficiency specifically in chondrocytes during a juvenile stage. This genetic scoliosis model will be useful in studying how a disruption of a specific molecular pathway produces vertebral growth disturbance and juvenile scoliosis.
*Texas Scottish Rite Hospital for Children, Dallas, TX
†Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX
‡Department of Pathology, and Division of Biological Sciences, University of California San Diego, La Jolla, CA
§Department of Biochemistry, Rush University Medical Center, Chicago, IL; and
¶Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI.
Address correspondence and reprint requests to Nobuhiro Kamiya, MD, PhD, Texas Scottish Rite Hospital for Children, 2222 Welborn St, Dallas 75219, TX; E-mail: Nobby.Kamiya@tsrh.org
Acknowledgment date: March 7, 2013. First revision date: May 9, 2013. Acceptance date: June 21, 2013.
The manuscript submitted does not contain information about medical device(s)/drug(s).
Scoliosis Research Society New Investigator Research Grant Award (N. K.) and the Intramural Research Program of Texas Scottish Rite Hospital for Children (N. K.) funds were received to support this work.
Relevant financial activities outside the submitted work: grants/grants pending, payment for lectures, royalties and stock/stock options.