Uehara Shotaro, Uno Yasuhiro, Inoue Takashi, Sasaki Erika, Yamazaki Hiroshi
Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, 194-8543, Japan.
Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd, Kainan, Wakayama, Japan.
Biopharm Drug Dispos. 2018 Jan;39(1):59-63. doi: 10.1002/bdd.2111. Epub 2017 Dec 11.
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 ATP-dependent 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.
普通狨猴（Callithrix jacchus）已被公认为是药物开发临床前测试中一种有用的小型非人类灵长类动物模型。在本研究中，从狨猴肝脏组织中克隆了新型ATP依赖性外排转运蛋白ABCB1的cDNA。狨猴ABCB1 cDNA编码一个由1279个氨基酸残基组成的蛋白质（分子量 = 141.4 kDa），含有ATP结合盒（ABC）蛋白的特征区域、两个疏水跨膜区域和两个胞质核苷酸结合区域，与人类ABCB1相似。与狗、猪和啮齿动物等非灵长类物种（79 - 90%）相比，推导的氨基酸序列与人类ABCB1的氨基酸序列具有更高的同一性（95%）。使用来自灵长类动物、狗、猪和啮齿动物的ABCB1氨基酸序列进行系统发育分析表明，狨猴、食蟹猴、恒河猴和人类之间的ABCB1存在密切的进化关系。通过定量逆转录 - 聚合酶链反应进行的组织分布分析表明，狨猴ABCB1 mRNA在肾脏中含量最高，其次是小肠和肝脏，与人类ABCB1相似，并且通过免疫印迹法也检测到了这些组织中的狨猴ABCB1蛋白。这些结果表明，狨猴中ABCB1的一级结构和组织分布与人类相似，表明狨猴和人类之间ABCB1具有相似的分子特征。
