Paulusma C C, Bosma P J, Zaman G J, Bakker C T, Otter M, Scheffer G L, Scheper R J, Borst P, Oude Elferink R P
Department of Gastrointestinal and Liver Diseases, Center for Liver and Intestinal Research, Academic Medical Center, Amsterdam, Netherlands.
Science. 1996 Feb 23;271(5252):1126-8. doi: 10.1126/science.271.5252.1126.
The human Dubin-Johnson syndrome and its animal model, the TR(-) rat, are characterized by a chronic conjugated hyperbilirubinemia. TR(-) rats are defective in the canalicular multispecific organic anion transporter (cMOAT), which mediates hepatobiliary excretion of numerous organic anions. The complementary DNA for rat cmoat, a homolog of the human multidrug resistance gene (hMRP1), was isolated and shown to be expressed in the canalicular membrane of hepatocytes. In the TR(-) rat, a single-nucleotide deletion in this gene resulted in a reduced messenger RNA level and absence of the protein. It is likely that this mutation accounts for the TR(-) phenotype.
人类的杜宾-约翰逊综合征及其动物模型TR(-)大鼠的特征是慢性结合性高胆红素血症。TR(-)大鼠的胆小管多特异性有机阴离子转运体（cMOAT）存在缺陷，该转运体介导多种有机阴离子的肝胆排泄。大鼠cmoat的互补DNA（人类多药耐药基因（hMRP1）的同源物）被分离出来，并显示在肝细胞的胆小管膜中表达。在TR(-)大鼠中，该基因的单核苷酸缺失导致信使RNA水平降低且蛋白质缺失。这种突变很可能是TR(-)表型的原因。
