| http://purl.uniprot.org/citations/9419367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/9419367 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/9419367 | http://www.w3.org/2000/01/rdf-schema#comment | "Class III multidrug resistance (MDR) P-glycoproteins (P-gp), mdr2 in mice and MDR3 in man, mediate the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte. Mice with a disrupted mdr2 gene completely lack biliary phospholipid excretion and develop progressive liver disease, characterized histologically by portal inflammation, proliferation of the bile duct epithelium, and fibrosis. This disease phenotype is very similar to a subtype of progressive familial intrahepatic cholestasis, hallmarked by a high serum gamma-glutamyltransferase (gamma-GT) activity. We report immunohistochemistry for MDR3 P-gp, reverse transcription-coupled PCR sequence analysis, and genomic DNA analysis of MDR3 from two progressive familial intrahepatic cholestasis patients with high serum gamma-GT. Canalicular staining for MDR3 P-gp was negative in liver tissue of both patients. Reverse transcription-coupled PCR sequencing of the first patient's sequence demonstrated a homozygous 7-bp deletion, starting at codon 132, which results in a frameshift and introduces a stop codon 29 codons downstream. The second patient is homozygous for a nonsense mutation in codon 957 (C --> T) that introduces a stop codon (TGA). Our results demonstrate that mutations in the human MDR3 gene lead to progressive familial intrahepatic cholestasis with high serum gamma-GT. The histopathological picture in these patients is very similar to that in the corresponding mdr2(-/-) mouse, in which mdr2 P-gp deficiency induces complete absence of phospholipid in bile."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.95.1.282"xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.95.1.282"xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Bernard O."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Bernard O."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Cresteil D."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Cresteil D."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Desrochers M."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Desrochers M."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Jacquemin E."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Jacquemin E."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Deleuze J.-F."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Deleuze J.-F."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Hadchouel M."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Hadchouel M."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Sturm E."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Sturm E."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Bosma P.J."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Bosma P.J."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Burdelski M."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Burdelski M."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Aten J."xsd:string |
| http://purl.uniprot.org/citations/9419367 | http://purl.uniprot.org/core/author | "Aten J."xsd:string |