FIGURE 5

Man1a2 knockdown produces cilia defects in reciliating mouse respiratory epithelia. (A) Relative expression of Man1a2 in respiratory epithelia after siRNA transfection. (B) Control epithelia are well ciliated with well-coordinated ciliary beat with a full stroke (Supplementary Video 1). (C)Man1a2-siRNA-transfected respiratory epithelia exhibited very short cilia that were mostly immotile except for a few areas with slow dyskinetic ciliary beat with incomplete stroke (Supplementary Video 2). (D,E)Man1a2 knockout mice with lung involvement also exhibit liver inflammation. (D)Man1a2^+/+ liver shows a portal area with indistinct bile ducts, abundant extramedullary hematopoiesis (EMH, H&E x200), and minimal ductular reaction (Epcam x200). The lung shows expanded alveoli and thin interalveolar septa. (E)Man1a2^–/– liver shows expanded portal areas with inflammation including EMH (H&E) and ductular reaction (Epcam x 200). The lung shows thick septa with sparse, unexpanded alveoli. The Man1a2^–/– liver transcriptome shows several dysregulated ciliary genes, including Dnah11 which causes PCD (Table 2 and Supplementary Table 10). (F,G). Dnah11^–/– mice with situs inversus also exhibit biliary inflammation. (F)Dnah11^+/+ mouse with normal location of heart and abdominal organs which includes two left and one right liver lobes, normal liver histology with EMH and some bile ducts in portal area. (G)Dnah11^–/– null mouse shows situs inversus with cardiac heterotaxy, inverted lobation of the liver (two right lobes), right-sided stomach and more centrally located spleen. Liver shows portal congestion and bile duct proliferation. All experiments were performed in triplicate.