Morphological changes in the vas deferens and expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in control, Delta F508 andknock-out CFTR mice during postnatal life

The morphology of the mouse vas deferens still undergoes major changes from birth to 40 days of age, such as differentiation of the mesenchymal cells into fibroblasts and muscle cells, differentiation of the epithelium into b asal and columnar epithelial cells, development of stereocilia, and the app earance of smooth endoplasmic reticulum organised in fingerprint-like struc tures or parallel, flattened saccules. In mutant. homozygous Delta F508 (De lta F/Delta F) and knock-out (cf/cf) CFTR mice, strain 129/FvB and 129/C57B L-6, respectively, a similar development occurred until the age of 20 days. At 40 days, however, the lumen was filled with eosinophilic secretions, an d sperm cells were absent in the majority of the animals examined, although sperm production in testis and epididymis appeared to be normal. CFTR was localised in the apical membrane and cytoplasm of the vas deferens epitheli um from 40 days on but could not be detected in the vas deferens before 20 days or in mutant adult CFTR mice as expected. Western blots of membrane pr eparations showed that the mature form of CFTR was present in vas deferens and testis but absent in seminal vesicles. Our results suggest that the fun ction of CFTR is probably essential after 20 days in the vas deferens and t hat its absence or dysfunction may-result in a vas deferens with a differen tiated epithelium but a collapsed lumen, which could at least temporarily d elay the transport of spermatozoa. These observations contrast with those m ade in the overall majority of CF patients. (C) 2000 Wiley-Liss, Inc.