title: Mutations in TJP2 cause progressive cholestatic liver disease.
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.
authors.affiliation: Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine, London, UK.
authors.forename: Melissa
authors.initials: M
authors.lastname: Sambrotta
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Strautnieks
authors.affiliation: Biomedical Research Centre (BRC) Genomics Core Facility, Guy's and St Thomas' National Health Service (NHS) Foundation Trust and King's College London, London, UK.
authors.forename: Efterpi
authors.initials: E
authors.lastname: Papouli
authors.affiliation: King's College Hospital NHS Foundation Trust, Department of Haematological Medicine, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Rushton
authors.affiliation: King's College Hospital NHS Foundation Trust, Department of Haematological Medicine, London, UK.
authors.forename: Barnaby E
authors.initials: BE
authors.lastname: Clark
authors.affiliation: Leeds Institute of Molecular Medicine, St James's University Hospital, University of Leeds, Leeds, UK.
authors.forename: David A
authors.identifier: 0000000303767736
authors.initials: DA
authors.lastname: Parry
authors.affiliation: Leeds Institute of Molecular Medicine, St James's University Hospital, University of Leeds, Leeds, UK.
authors.forename: Clare V
authors.identifier: 0000000343231602
authors.initials: CV
authors.lastname: Logan
authors.affiliation: Renal Sciences, Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine, London, UK.
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Newbury
authors.affiliation: 1] Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Binita M
authors.initials: BM
authors.lastname: Kamath
authors.affiliation: 1] Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Ling
authors.affiliation: 1] Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine, London, UK. [2] Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, UK.
authors.forename: Tassos
authors.initials: T
authors.lastname: Grammatikopoulos
authors.affiliation: Histopathology Department, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: Bart E
authors.initials: BE
authors.lastname: Wagner
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Magee
authors.affiliation: Department of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Sokol
authors.affiliation: 1] Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine, London, UK. [2] Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, UK.
authors.forename: Giorgina
authors.initials: G
authors.lastname: Mieli-Vergani
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Smith
authors.affiliation: Leeds Institute of Molecular Medicine, St James's University Hospital, University of Leeds, Leeds, UK.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Johnson
authors.affiliation: Children's Liver and Gastroenterology Unit, Leeds General Infirmary, Leeds, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: McClean
authors.affiliation: Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Simpson
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Knisely
authors.affiliation: 1] Liver Center Laboratory, Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Laura N
authors.initials: LN
authors.lastname: Bull
authors.affiliation: 1] Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine, London, UK. [2] Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Thompson
mesh_terms: D000818:Animals; D001483:Base Sequence; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000503:physiopathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment; D013045:Species Specificity; D019108:Tight Junctions / Q000235:genetics / Q000473:pathology*; D062827:Zonula Occludens-2 Protein / Q000235:genetics*
chemical_list: C569046:TJP2 protein, human; D062827:Zonula Occludens-2 Protein