Pathological changes in the lungs of Cux1 transgenic mice (834.1)

Abstract

Cux1 is a transcriptional repressor gene and part of the network controlling G1‐S phase transition. It represses the expression of the cyclin kinase inhibitors (CKI) p21 and p27. To determine the function of Cux1, we generated transgenic mice constitutively expressing Cux1. These mice develop multiorgan hyperplasia resulting from the aberrant repression of p27. We have previously characterized the changes in kidney development, spermatogenesis, and liver development in the Cux1 transgenic mice. In this study we have focused on the changes in the lung resulting from constitutive Cux1 expression. Histological staining of mice lung tissue showed extensive inflammation, localized areas of atelectasis alternated to emphysema, severe bronchiectasis, thickened bronchial basal membrane, and pluristratification of bronchial epithelium interspaced with areas of necrosis. Peribronchial arteries exhibited mild media thickening and enlarged adventitia with significant presence of fibroblasts (trichrome staining). The damage, bronchiectasis, and inflammation in particular were more evident in lungs of Cux1 transgenic mice. In conclusion, our results suggest that increased Cux1 expression results in multiple lung pathologies and may contribute to bronchiectasis.