Female mice lacking Pald1 exhibit endothelial cell apoptosis and emphysema

Isabel Egaña, Hiroshi Kaito, Anja Nitzsche, Lore Becker, Carolina Ballester-Lopez, Colin Niaudet, Milena Petkova, Wei Liu, Michael Vanlandewijck, Alexandra Vernaleken, Thomas Klopstock, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe De Angelis, Helge Rask-Andersen, Henrik J. Johansson, Janne Lehtiö, Liqun He, Ali Yildirim, Mats Hellström*Antonio Aguilar-Pimentel, Markus Ollert, Carsten Schmidt-Weber, Oana Amarie, Jochen Graw, Johannes Beckers, Lillian Garrett, Sabine M. Hölter, Annemarie Zimprich, Wolfgang Wurst, Kristin Moreth, Raffi Bekeredjian, Frauke Neff, Julia Calzada-Wack, Ildikó Rácz, Andreas Zimmer, Birgit Rathkolb, Eckhard Wolf, Jan Rozman, Martin Klingenspor, Tobias Stoeger, Oliver Eickelberg, Irina Treise, Dirk H. Busch, Manuela Östereicher, Ralph Steinkamp, Christoph Lengger, Holger Maier, Claudia Stoeger, Stefanie Leuchtenberger

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)


Paladin (Pald1, mKIAA1274 or x99384) was identified in screens for vascular-specific genes and is a putative phosphatase. Paladin has also been proposed to be involved in various biological processes such as insulin signaling, innate immunity and neural crest migration. To determine the role of paladin we have now characterized the Pald1 knock-out mouse in a broad array of behavioral, physiological and biochemical tests. Here, we show that female, but not male, Pald1 heterozygous and homozygous knock-out mice display an emphysema-like histology with increased alveolar air spaces and impaired lung function with an obstructive phenotype. In contrast to many other tissues where Pald1 is restricted to the vascular compartment, Pald1 is expressed in both the epithelial and mesenchymal compartments of the postnatal lung. However, in Pald1 knock-out females, there is a specific increase in apoptosis and proliferation of endothelial cells, but not in non-endothelial cells. This results in a transient reduction of endothelial cells in the maturing lung. Our data suggests that Pald1 is required during lung vascular development and for normal function of the developing and adult lung in a sex-specific manner. To our knowledge, this is the first report of a sex-specific effect on endothelial cell apoptosis.

Original languageEnglish
Article number15453
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Dec 2017


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