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Series GSE48443 Query DataSets for GSE48443
Status Public on Apr 06, 2014
Title Knockout mice reveal key roles for claudin-18 in alveolar fluid homeostasis.
Organism Mus musculus
Experiment type Expression profiling by array
Summary Claudin proteins are major constituents of epithelial and endothelial tight junctions (TJ), where they serve as regulators of paracellular permeability to ions and solutes. Claudin-18, a member of the large claudin family, is highly expressed in lung epithelium. To elucidate the role of claudin-18 in alveolar epithelial barrier function and fluid homeostasis, we generated claudin-18 knockout (C18 KO) mice. Increased alveolar fluid clearance (AFC) observed in C18 KO mice may have accounted for absence of lung edema despite increased alveolar solute permeability compared to wild type (WT) controls. Higher AFC in C18 KO mice was associated with higher Na-K-ATPase activity and increased expression of the Na-K-ATPase β1 subunit compared to WT controls. Consistent with in vivo findings, alveolar epithelial cell (AEC) monolayers derived from C18 KO mice exhibited lower transepithelial electrical resistance (RT) accompanied by increased solute and ion permeability without changes in ion selectivity. Expression of claudin-3 and claudin-4 was markedly increased in whole lung and in freshly isolated AEC from C18 KO mice, while claudin-5 was unchanged. In contrast, occludin, another major component of the TJ complex, was significantly decreased in C18 KO lung. Further analysis revealed rearrangements in the F-actin cytoskeleton in C18 KO MAECM. These findings demonstrate a crucial non-redundant role for claudin-18 in regulation of alveolar epithelial tight junction composition and permeability to ions and solutes. Importantly, increased AFC in C18 KO mice identifies additional roles for claudin-18 in alveolar fluid homeostasis beyond its direct contributions to barrier properties of the alveolar epithelium.
Overall design Animals with a ubiquitous knockout (C18 KO) were obtained by crossing mice harboring a conditional (floxed) allele of claudin-18 (Cldn18F/F) with CMV-cre deleter mice to delete exons 2 and 3 by Cre/loxP recombination.
Contributor(s) Li G, Flodby P, Luo J, Kage H, Sipos A, Gao D, Beard LL, Marconett CN, DeMaio L, Kim YH, Kim K, Laird-Offringa IA, Minoo P, Liebler JM, Zhou B, Crandall ED, Borok Z
Citation(s) 24588076
Submission date Jul 01, 2013
Last update date Jun 14, 2018
Contact name Crystal N Marconett
Phone 323-865-0649
Organization name University of Southern California
Department Biochemistry & Molecular Biology
Lab Crystal Marconett
Street address 1441 Eastlake Ave NOR 6418A
City Los Angeles
State/province CA
ZIP/Postal code 90089
Country USA
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (7)
GSM1178811 CLDN18_KnockOut_1
GSM1178812 CLDN18_KnockOut_2
GSM1178813 CLDN18_KnockOut_3
BioProject PRJNA210147

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Supplementary file Size Download File type/resource
GSE48443_RAW.tar 3.1 Mb (http)(custom) TAR
GSE48443_non_normalized.txt.gz 1.2 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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