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Sci Rep. 2017 Nov 13;7(1):15453. doi: 10.1038/s41598-017-14894-9.

Female mice lacking Pald1 exhibit endothelial cell apoptosis and emphysema.

Author information

1
Science for life laboratory, Department of Immunology, Genetics and Pathology, The Rudbeck laboratory, Uppsala University, Uppsala, Sweden.
2
INSERM U970, 56 rue Leblanc, F-75015, Paris, France.
3
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
4
Department of Neurology, Friedrich-Baur-Institut, Ludwig-Maximilians-Universität München, Munich, Germany.
5
Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), The German Center for Lung Research (DZL), Munich, Germany.
6
Department of Surgical Sciences, Head and Neck Surgery, Section of Otolaryngology, Uppsala University Hospital, Uppsala, Sweden.
7
German Center for Vertigo and Balance Disorders, Munich, Germany.
8
Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), Munich, Germany.
9
German Network for Mitochondrial Disorders (mitoNET), Munich, Germany.
10
Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technical University of Munich, Neuherberg, Germany.
11
German Center for Diabetes Research (DZD), Neuherberg, Germany.
12
Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
13
Science for life laboratory, Department of Immunology, Genetics and Pathology, The Rudbeck laboratory, Uppsala University, Uppsala, Sweden. mats.hellstrom@igp.uu.se.

Abstract

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.

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