Gene targeting of the cysteine peptidase cathepsin h impairs lung surfactant in mice.
12.10.2011
Bühling F, Kouadio M, Chwieralski CE, Kern U, Hohlfeld JM, Klemm N, Friedrichs N, Roth W, Deussing JM, Peters C, Reinheckel T
PLoS One. 2011;6(10):e26247
In vitro studies have demonstrated cathepsin H (Ctsh) involvement in the processing and secretion of the pulmonary surfactant protein B (SP-B). Furthermore, Ctsh is highly expressed in the secretory organelles of alveolar type II pneumocytes where the surfactant proteins are processed. Hence, we generated Ctsh null mice by gene targeting in embryonic stem cells. The targeting construct contains a ß-galactosidase (lacZ) reporter enabling the visualisation of Ctsh expression sites. Ctsh-deficiency was verified by northern blot, western blot, and measurement of the Ctsh aminopeptidase activity. Ctsh-/- mice show no gross phenotype and their development is normal without growth retardation. Broncho-alveolar lavage (BAL) from Ctsh-/- mice contained lower levels of SP-B indicating reduced SP-B secretion. The BAL phospholipid concentration was not different in Ctsh+/+ and Ctsh-/- mice, but measurement of surface tension by pulsating bubble surfactometry revealed an impairment of the tension reducing function of lung surfactant of Ctsh-/-mice.
