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

Full 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.

Author information

Author/s: Wang, Yingli (Y); Xiao, Ran (R); Yang, Fan (F); Karim, Baktiar O (BO); Iacovelli, Anthony J (AJ); Cai, Juanliang (J); Lerner, Charles P (CP); Richtsmeier, Joan T (JT); Leszl, Jen M (JM); Hill, Cheryl A (CA); Yu, Kai (K); Ornitz, David M (DM); Elisseeff, Jennifer (J); Huso, David L (DL); Jabs, Ethylin Wang (EW);

Affiliation: Institute of Genetic Medicine, Department of Pediatrics, The Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.

Grants: DE11441 (Agency:NIDCR NIH HHS) ; DE13078 (Agency:NIDCR NIH HHS) ; F33DE/HD05706 (Agency:NIDCR NIH HHS) ; HD24605 (Agency:NICHD NIH HHS) ; HD38384 (Agency:NICHD NIH HHS) ; HD39952 (Agency:NICHD NIH HHS) ; RR00171 (Agency:NCRR NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.

Journal: Development (Cambridge, England) (Development), published in England. (Language: eng)

Reference: 2005-Aug; vol 132 (issue 15) : pp 3537-48

Dates: Created 2005/07/14; Completed 2005/10/18; Revised 2007/11/14;

PMID: 15975938, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Acrocephalosyndactylia - genetics
Amino Acid Substitution
Animals
Bone Development
Bone and Bones - abnormalities
Cartilage - abnormalities; growth & development
Disease Models, Animal
Exons

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Receptors, Fibroblast Growth Factor (0) ; FGFR2 protein, human (EC 2.7.1.112) ; Fgfr2 protein, mouse (EC 2.7.1.112) ; Receptor Protein-Tyrosine Kinases (EC 2.7.1.112) ; Receptor, Fibroblast Growth Factor, Type 2 (EC 2.7.1.112)

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