title: Analysis of gene expression for microminipig liver transcriptomes using parallel long-read technology and short-read sequencing.
abstract: The microminipig is one of the smallest minipigs that has emerged as a possible experimental animal model, because it shares many anatomical and/or physiological similarities with humans, including the coronary artery distribution in the heart, the digestive physiology, the kidney size and its structure, and so on. However, information on gene expression profiles, including those on drug-metabolizing phase I and II enzymes, in the microminipig is limited. Therefore, the aim of the present study was to identify transcripts in microminipig livers and to determine gene expression profiles. De novo assembly and expression analyses of microminipig transcripts were conducted with liver samples from three male and three female microminipigs using parallel long-read and short-read sequencing technologies. After unique sequences had been automatically aligned by assembling software, the mean contig length of 50843 transcripts was 707 bp. The expression profiles of cytochrome P450 (P450) 1A2, 2C, 2E1 and 3A genes in livers in microminipigs were similar to those in humans. Liver carboxylesterase (CES) precursor, liver CES-like, UDP-glucuronosyltransferase (UGT) 2C1-like, amine sulfotransferase (SULT)-like, N-acetyltransferases (NAT8) and glutathione S-transferase (GST) A2 genes, which are relatively unknown genes in pigs and/or humans, were expressed strongly. Furthermore, no significant gender differences were observed in the gene expression profiles of phase I enzymes, whereas UGT2B17, SULT1E1, SULT2A1, amine SULT-like, NAT8 and GSTT4 genes were different between males and females among phase II enzyme genes under the present sample conditions. These results provide a foundation for mechanistic studies and the use of microminipigs as model animals for drug development in the future. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, 248-8555, Japan.
authors.forename: Chizuka
authors.initials: C
authors.lastname: Sakai
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, 248-8555, Japan.|Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Iwano
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Eurofins Genomics K.K., Ohta-ku, Tokyo, 143-0003, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Onodera
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, 248-8555, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Uchida
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, 248-8555, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Sakurada
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, 248-8555, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, 248-8555, Japan.
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Asaoka
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, 248-8555, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Imura
authors.affiliation: Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd, Kainan, Wakayama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Uno
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Japan.
authors.forename: Norie
authors.initials: N
authors.lastname: Murayama
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, 248-8555, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hayashi
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: Pharmaceutical Clinical Research Department, Toray Industries, Inc., 1-1, Nihonbashi-muromachi 2-chome, Chuo-ku, Tokyo, 103-8666, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D043182:Carboxylesterase / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D063990:Gene Ontology; D008099:Liver / Q000378:metabolism*; D008297:Male; D010088:Oxidoreductases / Q000235:genetics; D012313:RNA / Q000235:genetics; D017422:Sequence Analysis, DNA; D013552:Swine; D013556:Swine, Miniature / Q000235:genetics*; D059467:Transcriptome; D014166:Transferases / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D012313:RNA; D010088:Oxidoreductases; D014166:Transferases; D043182:Carboxylesterase