Altered gene expression in the lower respiratory tract of Car6 (-/-) mice.

From birth, the respiratory tract mucosa is exposed to various chemical, physical, and microbiological stress factors. Efficient defense mechanisms and strictly regulated renewal systems in the mucosa are thus required. Carbonic anhydrase VI (CA VI) is the only secreted isoenzyme of the α-CA gene family. It is transported in high concentrations in saliva and milk into the alimentary tract where it contributes to optimal pH homeostasis. Earlier study of transcriptomic responses of Car6 (-/-) mice has shown changes in the response to oxidative stress and brown fat cell differentiation in the submandibular gland. It has been suggested that CA VI delivered to the mucosal surface of the bronchiolar epithelium is an essential factor in defense and renewal of the lining epithelium. In this study, the transcriptional effects of CA VI deficiency were investigated in both trachea and lung of Car6 (-/-) mice using a cDNA microarray analysis. Functional clustering of the results indicated significant changes of gene transcription in the lower airways. The altered biological processes included antigen transport by M-cells, potassium transport, muscle contraction, and thyroid hormone synthesis. Immunohistochemical staining confirmed the absence of CA VI in the submandibular gland of Car6 (-/-) mice. Immunostaining of the trachea and lung samples revealed no differences between the knockout and wild type groups nor were any morphological changes observed. The present findings can help us to recognize novel functions for CA VI-one of the major protein constituents of saliva and milk.