Mutations in TJP2 cause progressive cholestatic liver disease.

TitleMutations in TJP2 cause progressive cholestatic liver disease.
Publication TypeJournal Article
Year of Publication2014
AuthorsSambrotta, M, Strautnieks, S, Papouli, E, Rushton, P, Clark, BE, Parry, DA, Logan, CV, Newbury, LJ, Kamath, BM, Ling, S, Grammatikopoulos, T, Wagner, BE, Magee, JC, Sokol, RJ, Mieli-Vergani, G, Smith, JD, Johnson, CA, McClean, P, Simpson, MA, Knisely, AS, Bull, LN, Thompson, RJ
Corporate AuthorsUniversity of Washington Center for Mendelian Genomics
JournalNat Genet
Volume46
Issue4
Pagination326-8
Date Published2014 Apr
ISSN1546-1718
KeywordsAnimals, Base Sequence, Cholestasis, Intrahepatic, High-Throughput Nucleotide Sequencing, Humans, Immunoblotting, Immunohistochemistry, Mice, Mice, Knockout, Microscopy, Electron, Transmission, Models, Biological, Molecular Sequence Data, Mutation, Pedigree, Real-Time Polymerase Chain Reaction, Sequence Alignment, Species Specificity, Tight Junctions, Zonula Occludens-2 Protein
Abstract

Elucidating genetic causes of cholestasis has proved to be important in understanding the physiology and pathophysiology of the liver. Here we show that protein-truncating mutations in the tight junction protein 2 gene (TJP2) cause failure of protein localization and disruption of tight-junction structure, leading to severe cholestatic liver disease. These findings contrast with those in the embryonic-lethal knockout mouse, highlighting differences in redundancy in junctional complexes between organs and species.

DOI10.1038/ng.2918
Alternate JournalNat. Genet.
PubMed ID24614073
PubMed Central IDPMC4061468
Grant ListU54 HG006493 / HG / NHGRI NIH HHS / United States
R56 DK094828 / DK / NIDDK NIH HHS / United States
U01 DK062453 / DK / NIDDK NIH HHS / United States
P30 DK026743 / DK / NIDDK NIH HHS / United States
UL1 TR000154 / TR / NCATS NIH HHS / United States
R01 DK094828 / DK / NIDDK NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
U01 DK062456 / DK / NIDDK NIH HHS / United States
1U54HG006493 / HG / NHGRI NIH HHS / United States
U01 DK062500 / DK / NIDDK NIH HHS / United States