Abnormalities in cartilage and bone development in the Apert syndrome FGFR2+/S252W mouse

Yingli Wang, Ran Xiao, Fan Yang, Baktiar O. Karim, Anthony J. Iacovelli, Juanliang Cai, Charles P. Lerner, Joan Therese Richtsmeier, Jen M. Leszl, Cheryl A. Hill, Kai Yu, David M. Ornitz, Jennifer Elisseff, David L. Huso, Ethylin Wang Jabs

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Apert syndrome is an autosomal dominant disorder characterized by malformations of the skull, limbs and viscera. Two-thirds of affected individuals have a S252W mutation in fibroblast growth factor receptor 2 (FGFR2). To study the pathogenesis of this condition, we generated a knock-in mouse model with this mutation. The Fgfr2+/S252W mutant mice have abnormalities of the skeleton, as well as of other organs including the brain, thymus, lungs, heart and intestines. In the mutant neurocranium, we found a midline sutural defect and craniosynostosis with abnormal osteoblastic proliferation and differentiation. We noted ectopic cartilage at the midline sagittal suture, and cartilage abnormalities in the basicranium, nasal turbinates and trachea. In addition, from the mutant long bones, in vitro cell cultures grown in osteogenic medium revealed chondrocytes, which were absent in the controls. Our results suggest that altered cartilage and bone development play a significant role in the pathogenesis of the Apert syndrome phenotype.

Original languageEnglish (US)
Pages (from-to)3537-3548
Number of pages12
JournalDevelopment
Volume132
Issue number15
DOIs
StatePublished - Aug 1 2005

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Acrocephalosyndactylia
Bone Development
Cartilage
Receptor, Fibroblast Growth Factor, Type 2
Craniosynostoses
Turbinates
Mutation
Viscera
Skull Base
Chondrocytes
Trachea
Nose
Skull
Skeleton
Thymus Gland
Sutures
Intestines
Extremities
Cell Culture Techniques
Phenotype

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Cite this

Wang, Y., Xiao, R., Yang, F., Karim, B. O., Iacovelli, A. J., Cai, J., ... Jabs, E. W. (2005). Abnormalities in cartilage and bone development in the Apert syndrome FGFR2+/S252W mouse. Development, 132(15), 3537-3548. https://doi.org/10.1242/dev.01914
Wang, Yingli ; Xiao, Ran ; Yang, Fan ; Karim, Baktiar O. ; Iacovelli, Anthony J. ; Cai, Juanliang ; Lerner, Charles P. ; Richtsmeier, Joan Therese ; Leszl, Jen M. ; Hill, Cheryl A. ; Yu, Kai ; Ornitz, David M. ; Elisseff, Jennifer ; Huso, David L. ; Jabs, Ethylin Wang. / Abnormalities in cartilage and bone development in the Apert syndrome FGFR2+/S252W mouse. In: Development. 2005 ; Vol. 132, No. 15. pp. 3537-3548.
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abstract = "Apert syndrome is an autosomal dominant disorder characterized by malformations of the skull, limbs and viscera. Two-thirds of affected individuals have a S252W mutation in fibroblast growth factor receptor 2 (FGFR2). To study the pathogenesis of this condition, we generated a knock-in mouse model with this mutation. The Fgfr2+/S252W mutant mice have abnormalities of the skeleton, as well as of other organs including the brain, thymus, lungs, heart and intestines. In the mutant neurocranium, we found a midline sutural defect and craniosynostosis with abnormal osteoblastic proliferation and differentiation. We noted ectopic cartilage at the midline sagittal suture, and cartilage abnormalities in the basicranium, nasal turbinates and trachea. In addition, from the mutant long bones, in vitro cell cultures grown in osteogenic medium revealed chondrocytes, which were absent in the controls. Our results suggest that altered cartilage and bone development play a significant role in the pathogenesis of the Apert syndrome phenotype.",
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Wang, Y, Xiao, R, Yang, F, Karim, BO, Iacovelli, AJ, Cai, J, Lerner, CP, Richtsmeier, JT, Leszl, JM, Hill, CA, Yu, K, Ornitz, DM, Elisseff, J, Huso, DL & Jabs, EW 2005, 'Abnormalities in cartilage and bone development in the Apert syndrome FGFR2+/S252W mouse', Development, vol. 132, no. 15, pp. 3537-3548. https://doi.org/10.1242/dev.01914

Abnormalities in cartilage and bone development in the Apert syndrome FGFR2+/S252W mouse. / Wang, Yingli; Xiao, Ran; Yang, Fan; Karim, Baktiar O.; Iacovelli, Anthony J.; Cai, Juanliang; Lerner, Charles P.; Richtsmeier, Joan Therese; Leszl, Jen M.; Hill, Cheryl A.; Yu, Kai; Ornitz, David M.; Elisseff, Jennifer; Huso, David L.; Jabs, Ethylin Wang.

In: Development, Vol. 132, No. 15, 01.08.2005, p. 3537-3548.

Research output: Contribution to journalArticle

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T1 - Abnormalities in cartilage and bone development in the Apert syndrome FGFR2+/S252W mouse

AU - Wang, Yingli

AU - Xiao, Ran

AU - Yang, Fan

AU - Karim, Baktiar O.

AU - Iacovelli, Anthony J.

AU - Cai, Juanliang

AU - Lerner, Charles P.

AU - Richtsmeier, Joan Therese

AU - Leszl, Jen M.

AU - Hill, Cheryl A.

AU - Yu, Kai

AU - Ornitz, David M.

AU - Elisseff, Jennifer

AU - Huso, David L.

AU - Jabs, Ethylin Wang

PY - 2005/8/1

Y1 - 2005/8/1

N2 - Apert syndrome is an autosomal dominant disorder characterized by malformations of the skull, limbs and viscera. Two-thirds of affected individuals have a S252W mutation in fibroblast growth factor receptor 2 (FGFR2). To study the pathogenesis of this condition, we generated a knock-in mouse model with this mutation. The Fgfr2+/S252W mutant mice have abnormalities of the skeleton, as well as of other organs including the brain, thymus, lungs, heart and intestines. In the mutant neurocranium, we found a midline sutural defect and craniosynostosis with abnormal osteoblastic proliferation and differentiation. We noted ectopic cartilage at the midline sagittal suture, and cartilage abnormalities in the basicranium, nasal turbinates and trachea. In addition, from the mutant long bones, in vitro cell cultures grown in osteogenic medium revealed chondrocytes, which were absent in the controls. Our results suggest that altered cartilage and bone development play a significant role in the pathogenesis of the Apert syndrome phenotype.

AB - Apert syndrome is an autosomal dominant disorder characterized by malformations of the skull, limbs and viscera. Two-thirds of affected individuals have a S252W mutation in fibroblast growth factor receptor 2 (FGFR2). To study the pathogenesis of this condition, we generated a knock-in mouse model with this mutation. The Fgfr2+/S252W mutant mice have abnormalities of the skeleton, as well as of other organs including the brain, thymus, lungs, heart and intestines. In the mutant neurocranium, we found a midline sutural defect and craniosynostosis with abnormal osteoblastic proliferation and differentiation. We noted ectopic cartilage at the midline sagittal suture, and cartilage abnormalities in the basicranium, nasal turbinates and trachea. In addition, from the mutant long bones, in vitro cell cultures grown in osteogenic medium revealed chondrocytes, which were absent in the controls. Our results suggest that altered cartilage and bone development play a significant role in the pathogenesis of the Apert syndrome phenotype.

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Wang Y, Xiao R, Yang F, Karim BO, Iacovelli AJ, Cai J et al. Abnormalities in cartilage and bone development in the Apert syndrome FGFR2+/S252W mouse. Development. 2005 Aug 1;132(15):3537-3548. https://doi.org/10.1242/dev.01914