{"doi":"10.1073/pnas.95.8.4544","title":"Low density lipoprotein receptor-negative mice expressing human apolipoprotein B-100 develop complex atherosclerotic lesions on a chow diet: No accentuation by apolipoprotein(a)","abstract":"<jats:p>\n                    We have generated mice with markedly elevated plasma levels of human low density lipoprotein (LDL) and reduced plasma levels of high density lipoprotein. These mice have no functional LDL receptors [\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ] and express a human apolipoprotein B-100 (apoB) transgene [\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    )] with or without an apo(a) transgene [\n                    <jats:italic>Tg(apoa</jats:italic>\n                    <jats:sup>+/−</jats:sup>\n                    )]. Twenty animals (10 males and 10 females) of each of the following four genotypes were maintained on a chow diet: (\n                    <jats:italic>i</jats:italic>\n                    )\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    , (\n                    <jats:italic>ii</jats:italic>\n                    )\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoa</jats:italic>\n                    <jats:sup>+/−</jats:sup>\n                    <jats:italic>), (iii</jats:italic>\n                    )\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>),</jats:italic>\n                    and (\n                    <jats:italic>iv</jats:italic>\n                    )\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>);Tg(apo</jats:italic>\n                    <jats:sup>+/−</jats:sup>\n                    <jats:italic>).</jats:italic>\n                    The mice were killed at 6 mo, and the percent area of the aortic intimal surface that stained positive for neutral lipid was quantified. Mean percent areas of lipid staining were not significantly different between the\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    and\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoa</jats:italic>\n                    <jats:sup>+/−</jats:sup>\n                    <jats:italic>)</jats:italic>\n                    mice (1.0 ± 0.2% vs. 1.4 ± 0.3%). However, the\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>)</jats:italic>\n                    mice had ≈15-fold greater mean lesion area than the\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    mice. No significant difference was found in percent lesion area in the\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>)</jats:italic>\n                    mice whether or not they expressed apo(a) [18.5 ± 2.5%, without lipoprotein(a), Lp(a), vs. 16.0 ± 1.7%, with Lp(a)]. Histochemical analyses of the sections from the proximal aorta of\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>)</jats:italic>\n                    mice revealed large, complex, lipid-laden atherosclerotic lesions that stained intensely with human apoB-100 antibodies. In mice expressing Lp(a), large amounts of apo(a) protein colocalized with apoB-100 in the lesions. We conclude that\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>)</jats:italic>\n                    mice exhibit accelerated atherosclerosis on a chow diet and thus provide an excellent animal model in which to study atherosclerosis. We found no evidence that apo(a) increased atherosclerosis in this animal model.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":1998,"id":594957,"datarank":0.7515952941144385,"base_score":5.0106352940962555,"endowment":5.0106352940962555,"self_citation_contribution":0.7515952941144385,"citation_network_contribution":0.0,"self_endowment_contribution":0.7515952941144385,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":149,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1523272,"name":"D. L. Newland","orcid":null,"position":1,"is_corresponding":false},{"id":543416,"name":"R. Tao","orcid":null,"position":2,"is_corresponding":false},{"id":532611,"name":"S. Marcovina","orcid":null,"position":3,"is_corresponding":false},{"id":1412558,"name":"J. Wang","orcid":"0000-0003-4331-6243","position":4,"is_corresponding":false},{"id":394195,"name":"V. Mooser","orcid":null,"position":5,"is_corresponding":false},{"id":1523273,"name":"R. E. Hammer","orcid":null,"position":6,"is_corresponding":false},{"id":1523274,"name":"H. H. Hobbs","orcid":null,"position":7,"is_corresponding":false},{"id":1523271,"name":"D. A. Sanan","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Low density lipoprotein receptor-negative mice expressing human apolipoprotein B-100 develop complex atherosclerotic lesions on a chow diet: No accentuation by apolipoprotein(a)","abstract":"<jats:p>\n                    We have generated mice with markedly elevated plasma levels of human low density lipoprotein (LDL) and reduced plasma levels of high density lipoprotein. These mice have no functional LDL receptors [\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ] and express a human apolipoprotein B-100 (apoB) transgene [\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    )] with or without an apo(a) transgene [\n                    <jats:italic>Tg(apoa</jats:italic>\n                    <jats:sup>+/−</jats:sup>\n                    )]. Twenty animals (10 males and 10 females) of each of the following four genotypes were maintained on a chow diet: (\n                    <jats:italic>i</jats:italic>\n                    )\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    , (\n                    <jats:italic>ii</jats:italic>\n                    )\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoa</jats:italic>\n                    <jats:sup>+/−</jats:sup>\n                    <jats:italic>), (iii</jats:italic>\n                    )\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>),</jats:italic>\n                    and (\n                    <jats:italic>iv</jats:italic>\n                    )\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>);Tg(apo</jats:italic>\n                    <jats:sup>+/−</jats:sup>\n                    <jats:italic>).</jats:italic>\n                    The mice were killed at 6 mo, and the percent area of the aortic intimal surface that stained positive for neutral lipid was quantified. Mean percent areas of lipid staining were not significantly different between the\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    and\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoa</jats:italic>\n                    <jats:sup>+/−</jats:sup>\n                    <jats:italic>)</jats:italic>\n                    mice (1.0 ± 0.2% vs. 1.4 ± 0.3%). However, the\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>)</jats:italic>\n                    mice had ≈15-fold greater mean lesion area than the\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    mice. No significant difference was found in percent lesion area in the\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>)</jats:italic>\n                    mice whether or not they expressed apo(a) [18.5 ± 2.5%, without lipoprotein(a), Lp(a), vs. 16.0 ± 1.7%, with Lp(a)]. Histochemical analyses of the sections from the proximal aorta of\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>)</jats:italic>\n                    mice revealed large, complex, lipid-laden atherosclerotic lesions that stained intensely with human apoB-100 antibodies. In mice expressing Lp(a), large amounts of apo(a) protein colocalized with apoB-100 in the lesions. We conclude that\n                    <jats:italic>LDLR</jats:italic>\n                    <jats:sup>−/−</jats:sup>\n                    ;\n                    <jats:italic>Tg(apoB</jats:italic>\n                    <jats:sup>+/+</jats:sup>\n                    <jats:italic>)</jats:italic>\n                    mice exhibit accelerated atherosclerosis on a chow diet and thus provide an excellent animal model in which to study atherosclerosis. We found no evidence that apo(a) increased atherosclerosis in this animal model.\n                  </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23304386","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":null,"oa_locations":[{"url":"https://pnas.org/doi/pdf/10.1073/pnas.95.8.4544","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/22526","host_type":"repository"}],"fields_of_study":[],"mesh_terms":[],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T16:03:02.197418Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}