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Spine (Phila Pa 1976). 2013 Oct 1;38(21):E1307-12. doi: 10.1097/BRS.0b013e3182a3d370.

Induction of SHP2 deficiency in chondrocytes causes severe scoliosis and kyphosis in mice.

Author information

1
*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.

Abstract

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.

PMID:
23873233
PMCID:
PMC3864111
DOI:
10.1097/BRS.0b013e3182a3d370
[Indexed for MEDLINE]
Free PMC Article

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