The transmembrane protein TMEM16A is required for normal development of the murine trachea

被引:191
|
作者
Rock, Jason R. [1 ]
Futtner, Christopher R. [1 ]
Harfe, Brian D. [1 ]
机构
[1] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA
关键词
mouse; Tmem16a; TMEM16; trachea; epithelium; cartilage; tracheomalacia; knockout; trachealis; muscle; smooth muscle;
D O I
10.1016/j.ydbio.2008.06.009
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pathological collapsibility of the upper airways, caused by many different genetic and environmental insults. is known as tracheomalacia in humans. We determined that Tmem16a, a member of an evolutionarily conserved family of predicted transmembrane proteins, is expressed in the developing trachea. We report that all mice homozygous for a null allele of Tmem16a died within one month of birth and exhibited severe tracheomalacia with gaps in the tracheal cartilage rings along the entire length of the trachea. In addition, the development of the trachealis Muscle that spans the dorsal aspect of the trachea was abnormal in Tmem16a mutants. Since the chondrogenic mesenchyme does not express Tmem16a at any time, we propose that the cartilage ring defect observed in Tmem16a mutants is secondary to all expansion of the embryonic trachea that might result from improper stratification of the embryonic tracheal epithelium or the abnormal trachealis Muscle, Our data identify Tmem16a as a novel regulator of epithelial and smooth muscle cell Organization in murine development, This Mutant, the first knockout of a vertebrate TMEM16 family member, provides a mouse model of tracheomalacia. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:141 / 149
页数:9
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