{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:36:47Z","timestamp":1791545807602,"version":"4.3.4"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\u2014<\/jats:title>\n                    <jats:p>\n                      Atherosclerosis studies in\n                      <jats:italic>Ldlr<\/jats:italic>\n                      knockout mice require breeding to homozygosity and congenic status on C57BL6\/J background, a process that is both time and resource intensive. We aimed to develop a new method for generating atherosclerosis through somatic deletion of\n                      <jats:italic>Ldlr<\/jats:italic>\n                      in livers of adult mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Overexpression of PCSK9 (proprotein convertase subtilisin\/kexin type 9) is currently used to study atherosclerosis, which promotes degradation of LDLR (low-density lipoprotein receptor) in the liver. We sought to determine whether CRISPR\/Cas9 (clustered regularly interspaced short palindromic repeats-associated 9) could also be used to generate atherosclerosis through genetic disruption of\n                      <jats:italic>Ldlr<\/jats:italic>\n                      in adult mice. We engineered adeno-associated viral (AAV) vectors expressing\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      Cas9 and a guide RNA targeting the\n                      <jats:italic>Ldlr<\/jats:italic>\n                      gene (AAV-CRISPR). Both male and female mice received either (1) saline, (2) AAV-CRISPR, or (3) AAV-hPCSK9 (human PCSK9)-D374Y. A fourth group of germline\n                      <jats:italic>Ldlr-KO<\/jats:italic>\n                      mice was included for comparison. Mice were placed on a Western diet and followed for 20 weeks to assess plasma lipids, PCSK9 protein levels, atherosclerosis, and editing efficiency. Disruption of\n                      <jats:italic>Ldlr<\/jats:italic>\n                      with AAV-CRISPR was robust, resulting in severe hypercholesterolemia and atherosclerotic lesions in the aorta. AAV-hPCSK9 also produced hypercholesterolemia and atherosclerosis as expected. Notable sexual dimorphism was observed, wherein AAV-CRISPR was superior for\n                      <jats:italic>Ldlr<\/jats:italic>\n                      removal in male mice, while AAV-hPCSK9 was more effective in female mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>\n                      This all-in-one AAV-CRISPR vector targeting\n                      <jats:italic>Ldlr<\/jats:italic>\n                      is an effective and versatile tool to model atherosclerosis with a single injection and provides a useful alternative to the use of germline\n                      <jats:italic>Ldlr<\/jats:italic>\n                      -KO mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.118.311221","type":"journal-article","created":{"date-parts":[[2018,7,19]],"date-time":"2018-07-19T05:16:37Z","timestamp":1531977397000},"page":"1997-2006","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":80,"title":["Somatic Editing of\n                    <i>Ldlr<\/i>\n                    With Adeno-Associated Viral-CRISPR Is an Efficient Tool for Atherosclerosis Research"],"prefix":"10.1161","volume":"38","author":[{"given":"Kelsey E.","family":"Jarrett","sequence":"first","affiliation":[{"name":"From the Department of Molecular Physiology and Biophysics (K.E.J., M.D.G., A.H., A.M.D., W.R.L.)"},{"name":"Integrative Molecular and Biomedical Sciences Graduate Program (K.E.J.), Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciaran","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Rice 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