{"corpus_id":33725718,"paper_sha":"1dec256257f5883714ebb7ec94679fed6b8036e9","doi":"10.1038/srep26942","arxiv_id":null,"pmid":27245873,"pmcid":"4887883","mag_id":2412230493,"dblp_id":null,"acl_id":null,"title":"Hyperlipidemia-associated gene variations and expression patterns revealed by whole-genome and transcriptome sequencing of rabbit models","year":2016,"publication_date":"2016-06-01","venue":"Scientific Reports","journal":{"name":"Scientific Reports","pages":null,"volume":"6"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":53,"citation_count":28,"influential_citation_count":1,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Aorta","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D001011"},{"d":"Atherosclerosis","mj":false,"qs":[{"q":"chemically induced","mj":false,"ui":"Q000139"},{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D050197"},{"d":"Cholesterol","mj":false,"qs":[{"q":"administration & dosage","mj":false,"ui":"Q000008"}],"ui":"D002784"},{"d":"Diet, High-Fat","mj":false,"qs":[{"q":"adverse effects","mj":true,"ui":"Q000009"}],"ui":"D059305"},{"d":"Disease Models, Animal","mj":false,"ui":"D004195"},{"d":"Gene Expression","mj":false,"ui":"D015870"},{"d":"Genetic Variation","mj":true,"ui":"D014644"},{"d":"Genome","mj":true,"ui":"D016678"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Hypercholesterolemia","mj":false,"qs":[{"q":"chemically induced","mj":false,"ui":"Q000139"},{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D006937"},{"d":"Liver","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D008099"},{"d":"Molecular Sequence Annotation","mj":false,"ui":"D058977"},{"d":"Rabbits","mj":false,"ui":"D011817"},{"d":"Receptors, LDL","mj":false,"qs":[{"q":"deficiency","mj":false,"ui":"Q000172"},{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D011973"},{"d":"Transcriptome","mj":false,"ui":"D059467"},{"d":"Whole Genome Sequencing","mj":false,"ui":"D000073336"}],"chemicals":[{"n":"Receptors, LDL","ui":"D011973","reg":"0"},{"n":"Cholesterol","ui":"D002784","reg":"97C5T2UQ7J"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.nature.com/articles/srep26942.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/f416774471899a2724478fa812e02e7c5e5ce0be","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"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.","claims":[{"public_id":"cl_591139378c6c6b519b7a7ef389737d0c","status":"active","text":"Cholesterol-rich diet-fed rabbits, but not WHHL rabbits, exhibit pronounced inflammatory responses and abnormal lipid metabolism in the liver.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_591139378c6c6b519b7a7ef389737d0c"},{"public_id":"cl_b2a763d2e0fca4f492cd87103812f92d","status":"active","text":"Gene expression profiles of WHHL rabbits and cholesterol-rich diet-fed NZW rabbits are essentially similar in the aorta despite different types of hypercholesterolemia.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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