Title | Mutations in TJP2 cause progressive cholestatic liver disease. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Sambrotta, 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 Authors | University of Washington Center for Mendelian Genomics |
Journal | Nat Genet |
Volume | 46 |
Issue | 4 |
Pagination | 326-8 |
Date Published | 2014 Apr |
ISSN | 1546-1718 |
Keywords | Animals, 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. |
DOI | 10.1038/ng.2918 |
Alternate Journal | Nat. Genet. |
PubMed ID | 24614073 |
PubMed Central ID | PMC4061468 |
Grant List | U54 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 |