Molecular cloning and tissue distribution of a novel marmoset ABC transporter

Abstract

Common marmosets (Callithrix jacchus) have been recognized as a useful small non-human primate model in preclinical testing for drug development. In this study, a cDNA of novel ATPdependent efflux transporter ABCB1 was cloned from marmoset liver tissue. Marmoset ABCB1 cDNA encodes a protein of 1279 amino acid residues (MW = 141.4 kDa) containing characteristic regions of an ATP-binding cassette (ABC) protein, two hydrophobic transmembrane regions and two cytoplasmic nucleotide-binding regions, similar to human ABCB1. The deduced amino acid sequences were more highly identical (95%) to those of human ABCB1 compared with non-primate species such as dogs, pigs and rodents (79-90%). A close evolutionary relationship of ABCB1 among marmosets, cynomolgus and rhesus monkeys and humans was evident from a phylogenetic analysis using ABCB1 amino acid sequences from primates, dogs, pigs and rodents. Tissue distribution analyses by quantitative reverse transcription-polymerase chain reaction indicated that marmoset ABCB1 mRNA was most abundant in kidneys, followed by small intestines and livers, similar to human ABCB1, and marmoset ABCB1 proteins in these tissues were also detected by immunoblotting. These results indicated that the primary structure and tissue distribution of ABCB1 in marmosets were similar to those of humans, suggesting similar molecular characteristics of ABCB1 between marmosets and humans.

Survey of Drug Oxidation Activities in Hepatic and Intestinal Microsomes of Individual Common Marmosets, a New Nonhuman Primate Animal Model

“…We also found that marmoset pulmonary P450 2F1 oxidized biphenyl and 7-ethoxycoumarin [31], and kidney P450 4A11 is a ω-hydroxylase with respect to arachidonic acid and lauric acid [25]. Furthermore, data for marmosets regarding other important drug-metabolizing enzymes and transporters (e.g., flavin-containing monooxygenases [35], aldehyde oxidases [36], catechol- O -methyltransferase [37], and ABC transporters [38]) are now available. Investigations of marmoset UDP-glucuronosyltransferases, glutathione S -transferases, and carboxy esterases are ongoing projects to help elucidate drug metabolism and disposition in marmosets as a model animal.…”