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

Harry K W Kim, Olumide Aruwajoye, Daniel Sucato, B. Stephens Richards, Gen Sheng Feng, Di Chen, Philip D. King, Nobuhiro Kamiya

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 confi rmed 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-specifi c 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.

Original languageEnglish (US)
JournalSpine
Volume38
Issue number21
DOIs
StatePublished - Oct 1 2013

Fingerprint

Kyphosis
Scoliosis
Chondrocytes
Spine
Growth
Genetic Techniques
Osteophyte
Lordosis
Genetic Engineering
Growth Plate
Cartilage
Thorax
Animal Models
Tomography

Keywords

  • Adolescent
  • Age specifi c gene disruption
  • Cartilage
  • Chondrocyte
  • Conditional knockout
  • Kyphosis
  • Lordosis
  • Loss of function
  • Mouse model
  • Ras-mapk signal
  • Scoliosis
  • Shp2
  • Spine

ASJC Scopus subject areas

  • Clinical Neurology
  • Orthopedics and Sports Medicine

Cite this

Induction of SHP2 deficiency in chondrocytes causes severe scoliosis and kyphosis in mice. / Kim, Harry K W; Aruwajoye, Olumide; Sucato, Daniel; Richards, B. Stephens; Feng, Gen Sheng; Chen, Di; King, Philip D.; Kamiya, Nobuhiro.

In: Spine, Vol. 38, No. 21, 01.10.2013.

Research output: Contribution to journalArticle

Kim, Harry K W ; Aruwajoye, Olumide ; Sucato, Daniel ; Richards, B. Stephens ; Feng, Gen Sheng ; Chen, Di ; King, Philip D. ; Kamiya, Nobuhiro. / Induction of SHP2 deficiency in chondrocytes causes severe scoliosis and kyphosis in mice. In: Spine. 2013 ; Vol. 38, No. 21.
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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 confi rmed 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-specifi c 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.",
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T1 - Induction of SHP2 deficiency in chondrocytes causes severe scoliosis and kyphosis in mice

AU - Kim, Harry K W

AU - Aruwajoye, Olumide

AU - Sucato, Daniel

AU - Richards, B. Stephens

AU - Feng, Gen Sheng

AU - Chen, Di

AU - King, Philip D.

AU - Kamiya, Nobuhiro

PY - 2013/10/1

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N2 - 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 confi rmed 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-specifi c 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.

AB - 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 confi rmed 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-specifi c 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.

KW - Adolescent

KW - Age specifi c gene disruption

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KW - Chondrocyte

KW - Conditional knockout

KW - Kyphosis

KW - Lordosis

KW - Loss of function

KW - Mouse model

KW - Ras-mapk signal

KW - Scoliosis

KW - Shp2

KW - Spine

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