Skip Navigation LinksHome > October 01, 2013 - Volume 38 - Issue 21 > Induction of SHP2 Deficiency in Chondrocytes Causes Severe S...
doi: 10.1097/BRS.0b013e3182a3d370
Basic Science

Induction of SHP2 Deficiency in Chondrocytes Causes Severe Scoliosis and Kyphosis in Mice

Kim, Harry K. W. MD*,†; Aruwajoye, Olumide MS*; Sucato, Daniel MD*,†; Richards, B. Stephens MD*,†; Feng, Gen-Sheng PhD; Chen, Di MD, PhD§; King, Philip D. PhD; Kamiya, Nobuhiro MD, PhD*,†

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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

© 2013 by Lippincott Williams & Wilkins

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