Muc5b-deficient mice develop early histological lung abnormalities

Abstract

ABSTRACTGel-forming mucins are the main organic component responsible for physical properties of the mucus hydrogels. While numerous biological functions of these mucins are well documented, specific physiological functions of each mucin are largely unknown. To investigatein vivofunctions of the gel-forming mucin Muc5b, which is with Muc5ac the major secreted airway mucin, we generated mice in which Muc5b was disrupted and maintained in the absence of environmental stress. Adult Muc5b-deficient mice displayed bronchial hyperplasia and metaplasia, interstitial thickening, alveolar collapse, immune cell infiltrates, fragmented and disorganized elastin fibers and collagen deposits that were for approximately one fifth of mice associated with altered pulmonary function leading to respiratory failure. These lung abnormalities start early in life, as demonstrated for one fourth 2-day-old Muc5b-deficient pups. Thus, the mouse mucin Muc5b is essential for maintaining normal lung function.