title: Hyperlipidemia-associated gene variations and expression patterns revealed by whole-genome and transcriptome sequencing of rabbit models.
abstract: The rabbit (Oryctolagus cuniculus) is an important experimental animal for studying human diseases, such as hypercholesterolemia and atherosclerosis. Despite this, genetic information and RNA expression profiling of laboratory rabbits are lacking. Here, we characterized the whole-genome variants of three breeds of the most popular experimental rabbits, New Zealand White (NZW), Japanese White (JW) and Watanabe heritable hyperlipidemic (WHHL) rabbits. Although the genetic diversity of WHHL rabbits was relatively low, they accumulated a large proportion of high-frequency deleterious mutations due to the small population size. Some of the deleterious mutations were associated with the pathophysiology of WHHL rabbits in addition to the LDLR deficiency. Furthermore, we conducted transcriptome sequencing of different organs of both WHHL and cholesterol-rich diet (Chol)-fed NZW rabbits. We found that gene expression profiles of the two rabbit models were essentially similar in the aorta, even though they exhibited different types of hypercholesterolemia. In contrast, Chol-fed rabbits, but not WHHL rabbits, exhibited pronounced inflammatory responses and abnormal lipid metabolism in the liver. These results provide valuable insights into identifying therapeutic targets of hypercholesterolemia and atherosclerosis with rabbit models.
authors.affiliation: Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Niimi
authors.affiliation: Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Ding
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai, China.|School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Chen
authors.affiliation: Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Hongjiu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: EG Information Technology Enterprise (EGI), BasePair Biotechnology Co., Ltd., Shanghai, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Key Lab of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Key Lab of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Tuantuan
authors.initials: T
authors.lastname: Gui
authors.affiliation: Key Lab of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Shengdi
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Lab of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai, China.|School of Biotechnology, East China University of Science and Technology, Shanghai, China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai, China.|School of Life Science and Technology, Shanghai Tongji University, Shanghai, China.
authors.forename: Mushui
authors.initials: M
authors.lastname: Cao
authors.affiliation: Key Lab of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Lu
authors.affiliation: School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai, China.|School of Biotechnology, East China University of Science and Technology, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Lab of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Dongshan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Song
authors.affiliation: Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Shen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Bo
authors.initials: B
authors.lastname: Ning
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Ziyun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute for Experimental Animals, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Koike
authors.affiliation: Institute for Experimental Animals, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiomi
authors.affiliation: Research Institute of Atherosclerotic Disease and Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, China.|Department of Pathology, Xi'an Medical University, Xi'an, China.
authors.forename: Enqi
authors.initials: E
authors.lastname: Liu
authors.affiliation: Key Lab of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Luonan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.|Department of Pathology, Xi'an Medical University, Xi'an, China.
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
authors.affiliation: Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.affiliation: Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai, China.|School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai, China.|School of Biotechnology, East China University of Science and Technology, Shanghai, China.|School of Life Science and Technology, Shanghai Tongji University, Shanghai, China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000008:administration & dosage; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D015870:Gene Expression; D014644:Genetic Variation; D016678:Genome; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D058977:Molecular Sequence Annotation; D011817:Rabbits; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics*; D059467:Transcriptome; D000073336:Whole Genome Sequencing
chemical_list: D011973:Receptors, LDL; D002784:Cholesterol