Crouzon syndrome mouse model exhibits cartilage hyperproliferation and defective segmentation in the developing trachea

作     者：Elizabeth A. Hines Mary-Kayt N. Jones Julie F. Harvey Chad Perlyn David M. Ornitz Xin Sun Jamie M. Verheyden 

作者机构：Laboratory of GeneticsUniversity of WisconsinMadisonWI 53706USA Department of SurgeryFlorida International University College of MedicineMiamiFL 33199USA Department of Developmental BiologyWashington University School of MedicineSt. LouisMO 63110USA Department of PediatricsUniversity of California-San DiegoLa JollaCA 92093USA 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2019年第62卷第10期

页      面：1375-1380页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

基　　金：National Institute of Child Health and Human Development, NICHD, (R01HD049808) National Institute of Child Health and Human Development, NICHD 

主　　题：trachea lung mouse development 

摘      要：Crouzon syndrome is the result of a gain-of-function point mutation in FGFR2. Mimicking the human mutation, a mouse model of Crouzon syndrome(Fgfr2342Y) recapitulates patient deformities, including failed tracheal cartilage segmentation, resulting in a cartilaginous sleeve in the homozygous mutants. We found that the Fgfr2C342Y/C^342Y mutants exhibited an increase in chondrocytes prior to segmentation. This increase is due at least in part to over proliferation. Genetic ablation of chondrocytes in the mutant led to restoration of segmentation in the lateral but not central portion of the trachea. These results suggest that in the Fgfr2C342Y/C342Y mutants, increased cartilage cell proliferation precedes and contributes to the disruption of cartilage segmentation in the developing trachea.