Document Detail

A Pro253Arg mutation in fibroblast growth factor receptor 2 (Fgfr2) causes skeleton malformation mimicking human Apert syndrome by affecting both chondrogenesis and osteogenesis.
MedLine Citation:
PMID:  18242159     Owner:  NLM     Status:  MEDLINE    
Apert syndrome is one of the most severe craniosynostosis that is mainly caused by either a Ser252Trp(S252W) or Pro253Arg(P253R) mutation in fibroblast growth factor receptor 2 (FGFR2). As an autosomal dominant disorder, Apert syndrome is mainly characterized by skull malformation resulting from premature fusion of craniofacial sutures, as well as syndactyly, etc. A P253R mutation of FGFR2 results in nearly one-thirds of the cases of Apert syndrome. The pathogenesis of Apert syndrome resulting from P253R mutation of FGFR2 is still not fully understood. Here we reported a knock-in mouse model carrying P253R mutation in Fgfr2. The mutant mice exhibit smaller body size and brachycephaly. Analysis of the mutant skulls and long bones revealed premature fusion of coronal suture, shortened cranial base and growth plates of long bones. In vitro organ culture studies further revealed that, compared with wild-type littermates, the mutant mice have prematurely fused coronal sutures and retarded long bone growth. Treatment of the cultured calvaria and femur with PD98059, an Erk1/2 inhibitor, resulted in partially alleviated coronal suture fusion and growth retardation of femur respectively. Our data indicated that the P253R mutation in Fgfr2 directly affect intramembranous and endochondral ossification, which resulted in the premature closure of coronal sutures and growth retardation of long bones and cranial base. And the Erk1/2 signaling pathway partially mediated the effects of P253R mutation of Fgfr2 on cranial sutures and long bones.
Liangjun Yin; Xiaolan Du; Cuiling Li; Xiaoling Xu; Zhi Chen; Nan Su; Ling Zhao; Huabing Qi; Fubing Li; Jing Xue; Jing Yang; Min Jin; Chuxia Deng; Lin Chen
Related Documents :
18242159 - A pro253arg mutation in fibroblast growth factor receptor 2 (fgfr2) causes skeleton mal...
12393809 - Okihiro syndrome is caused by sall4 mutations.
16906569 - Patched mutations and hairy skin patches: a new sign in gorlin syndrome.
10353779 - Phenotypic findings of cowden syndrome and bannayan-zonana syndrome in a family associa...
15279809 - Nijmegen breakage syndrome: clinical manifestation of defective response to dna double-...
9726049 - Multiple synchronous lung cancers and atypical adenomatous hyperplasia in li-fraumeni s...
21984749 - Association between deletion size and important phenotypes expands the genomic region o...
871569 - The syndrome of capgras.
22975109 - Increased percentage of cd8+cd28- t cells correlates with clinical activity in primary ...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-01-31
Journal Detail:
Title:  Bone     Volume:  42     ISSN:  8756-3282     ISO Abbreviation:  Bone     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-21     Completed Date:  2008-05-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8504048     Medline TA:  Bone     Country:  United States    
Other Details:
Languages:  eng     Pagination:  631-43     Citation Subset:  IM    
State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Acrocephalosyndactylia / genetics,  metabolism*,  pathology*
Arginine / genetics,  metabolism
Cells, Cultured
Chondrogenesis* / genetics
Disease Models, Animal
MAP Kinase Signaling System
Mice, Transgenic
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Mutation / genetics
Ossification, Heterotopic / genetics,  metabolism,  pathology
Osteogenesis* / genetics
Proline / genetics,  metabolism
Receptor, Fibroblast Growth Factor, Type 2 / genetics,  metabolism*
Reg. No./Substance:
147-85-3/Proline; 74-79-3/Arginine; EC, Fibroblast Growth Factor, Type 2; EC Protein Kinase 1; EC Protein Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Ectopic thymic parathyroid adenoma and vitamin D deficiency rickets: a 5-year-follow-up case report ...
Next Document:  The investigation of recognition interaction between phenylboronate monolayer and glycated hemoglobi...