{"doi":"10.1161/hq0801.093864","title":"Mice Expressing Only the Mutant APOE3Leiden Gene Show Impaired VLDL Secretion","abstract":"<jats:p>Apolipoprotein E (apoE)-deficient mice develop hepatic steatosis and show impaired very low density lipoprotein (VLDL)-triglyceride (TG) secretion. These effects are normalized on the introduction of the human APOE3 gene. To assess whether this apoE effect is isoform specific, we studied hepatic lipid metabolism in mice expressing either APOE3 or the mutant APOE3Leiden on<jats:italic>apoe</jats:italic>−/− or<jats:italic>apoe+</jats:italic>/− backgrounds. The transgenes were expressed mainly in periportal hepatocytes, as revealed by in situ hybridization. Mice expressing APOE3Leiden, on the<jats:italic>apoe</jats:italic>−/− and<jats:italic>apoe+</jats:italic>/− backgrounds, had fatty livers, which were absent in APOE3/<jats:italic>apoe</jats:italic>−/− mice. APOE3Leiden/<jats:italic>apoe</jats:italic>−/− mice showed a strongly reduced VLDL-TG secretion compared with APOE3/<jats:italic>apoe</jats:italic>−/− mice (48±14 versus 82±10 μmol/kg per hour, respectively). The presence of a single mouse<jats:italic>apoe</jats:italic>allele increased VLDL-TG secretion in APOE3Leiden/<jats:italic>apoe+</jats:italic>/− mice (121±43 μ mol/kg per hour) compared with APOE3Leiden/<jats:italic>apoe</jats:italic>−/− mice. These results show that APOE3Leiden does not prevent development of a fatty liver and does not normalize VLDL-TG secretion in mice with an apoE-deficient background. The presence of a single mouse<jats:italic>apoe</jats:italic>allele is sufficient to normalize the APOE3Leiden-associated reduction of VLDL-TG secretion but does not prevent steatosis. We conclude that apoE-mediated stimulation of VLDL secretion is isoform specific.</jats:p>","journal":"Arteriosclerosis, Thrombosis, and Vascular Biology","year":2001,"id":633785,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"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":225859,"name":"Bas Teusink","orcid":"0000-0003-3929-0423","position":1,"is_corresponding":false},{"id":1643423,"name":"Julius F.W. Baller","orcid":null,"position":2,"is_corresponding":false},{"id":1643426,"name":"Henk Wolters","orcid":null,"position":3,"is_corresponding":false},{"id":1643427,"name":"Rick Havinga","orcid":null,"position":4,"is_corresponding":false},{"id":55371,"name":"Ko Willems van Dijk","orcid":"0000-0002-2172-7394","position":5,"is_corresponding":false},{"id":611566,"name":"Louis M. Havekes","orcid":null,"position":6,"is_corresponding":false},{"id":603383,"name":"Folkert Kuipers","orcid":"0000-0003-2518-737X","position":7,"is_corresponding":false},{"id":323597,"name":"Arjen R. Mensenkamp","orcid":"0000-0003-3805-877X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mice Expressing Only the Mutant APOE3Leiden Gene Show Impaired VLDL Secretion","abstract":"<jats:p>Apolipoprotein E (apoE)-deficient mice develop hepatic steatosis and show impaired very low density lipoprotein (VLDL)-triglyceride (TG) secretion. These effects are normalized on the introduction of the human APOE3 gene. To assess whether this apoE effect is isoform specific, we studied hepatic lipid metabolism in mice expressing either APOE3 or the mutant APOE3Leiden on<jats:italic>apoe</jats:italic>−/− or<jats:italic>apoe+</jats:italic>/− backgrounds. The transgenes were expressed mainly in periportal hepatocytes, as revealed by in situ hybridization. Mice expressing APOE3Leiden, on the<jats:italic>apoe</jats:italic>−/− and<jats:italic>apoe+</jats:italic>/− backgrounds, had fatty livers, which were absent in APOE3/<jats:italic>apoe</jats:italic>−/− mice. APOE3Leiden/<jats:italic>apoe</jats:italic>−/− mice showed a strongly reduced VLDL-TG secretion compared with APOE3/<jats:italic>apoe</jats:italic>−/− mice (48±14 versus 82±10 μmol/kg per hour, respectively). The presence of a single mouse<jats:italic>apoe</jats:italic>allele increased VLDL-TG secretion in APOE3Leiden/<jats:italic>apoe+</jats:italic>/− mice (121±43 μ mol/kg per hour) compared with APOE3Leiden/<jats:italic>apoe</jats:italic>−/− mice. These results show that APOE3Leiden does not prevent development of a fatty liver and does not normalize VLDL-TG secretion in mice with an apoE-deficient background. The presence of a single mouse<jats:italic>apoe</jats:italic>allele is sufficient to normalize the APOE3Leiden-associated reduction of VLDL-TG secretion but does not prevent steatosis. We conclude that apoE-mediated stimulation of VLDL secretion is isoform specific.</jats:p>","is_dataset_classified":null,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11498467","pmcid":null,"openalex_id":"https://openalex.org/W2117532223","authors":[],"funders":[],"total_grants":0,"fwci":0.7834,"citation_percentile":0.7041678,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2014,"count":1},{"year":2026,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.ahajournals.org/doi/pdf/10.1161/hq0801.093864","host_type":"journal"},{"url":"https://www.ahajournals.org/doi/pdf/10.1161/hq0801.093864","host_type":"publisher"},{"url":"https://www.ahajournals.org/doi/full/10.1161/hq0801.093864","host_type":"publisher"},{"url":"https://doi.org/10.1161/hq0801.093864","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11498467","host_type":"repository"},{"url":"https://research.rug.nl/en/publications/6273b7d3-a4c6-4431-91fe-ba004e874cf7","host_type":"repository"},{"url":"https://resolver.tno.nl/uuid:d91f96d9-e4aa-43f1-920c-e9ae67ae5170","host_type":"repository"},{"url":"https://hdl.handle.net/11370/6273b7d3-a4c6-4431-91fe-ba004e874cf7","host_type":"repository"},{"url":"http://resolver.tudelft.nl/uuid:d91f96d9-e4aa-43f1-920c-e9ae67ae5170","host_type":"repository"}],"fields_of_study":["Peroxisome Proliferator-Activated Receptors","Liver Disease Diagnosis and Treatment","Diabetes, Cardiovascular Risks, and Lipoproteins","Animals","Apolipoprotein E3","Apolipoproteins B","Apolipoproteins E","Fatty Liver","Lipid Metabolism","Lipoproteins, VLDL","Liver","Mice","Mice, Transgenic","Protein Isoforms","RNA, Messenger","Triglycerides"],"mesh_terms":["Animals","Apolipoproteins B","Apolipoproteins E","Fatty Liver","Lipoproteins, VLDL","Liver","Mice, Transgenic","RNA, Messenger","Triglycerides","Protein Isoforms","Lipid Metabolism","Mice","Apolipoprotein E3"],"keywords":["Apolipoprotein E","Very low-density lipoprotein","Endocrinology","Internal medicine","Steatosis","Apolipoprotein B","Triglyceride","Secretion","Biology","Lipoprotein","Allele","Genetically modified mouse","Transgene","Cholesterol","Medicine","Gene","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T12:39:22.236784Z","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":[]}