Regulation of the Muc5ac Gene in the Mouse Airway

University Of Tx Md Anderson Can Ctr, Houston TX

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): Mucus hyper-production and secretion are prominent features of many pulmonary diseases. This hyperproduction and secretion can lead to plugging of the airways and eventually death. Under normal conditions the small amount of mucus produced by the airway epithelium provides a viscoelastic barrier that acts as a primary defense against pathogens and noxious irritants. However, during airway inflammation, mucin synthesis is increased dramatically. During mucus metaplasia, Clara cells undergo a dramatic structural reorganization, but retain their essential molecular and functional phenotype of specialized apical secretory cells of the airway. We have determined that Clara cells are the cells that produce mucin in the airways of mice. MucSac is the major mucin gene that is induced during airway inflammation. Our lab has shown that the expression of MucSac is tightly constrained to Clara cells of the proximal airways. This proposal will test the ability of the 5' and 3' UTRs of the MucSac gene to regulate its expression. We will examine in vitro, regions in the 5' and 3' UTRs conserved between humans and mice. In vivo studies will then be used to verify the functional importance of these conserved regions in reporter mice. [unreadable] [unreadable] [unreadable]