{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:11:43Z","timestamp":1792177903451,"version":"4.4.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,4,11]]},"abstract":"<jats:p>\n                    Recently, the human ATP-binding cassette transporter-1 (ABC1) gene has been demonstrated to be mutated in patients with Tangier disease. To investigate the role of the ABC1 protein in an experimental\n                    <jats:italic>in vivo<\/jats:italic>\n                    model, we used gene targeting in DBA-1J embryonic stem cells to produce an ABC1-deficient mouse. Expression of the murine\n                    <jats:italic>Abc1<\/jats:italic>\n                    gene was ablated by using a nonisogenic targeting construct that deletes six exons coding for the first nucleotide-binding fold. Lipid profiles from\n                    <jats:italic>Abc1<\/jats:italic>\n                    knockout (\u2212\/\u2212) mice revealed an \u224870% reduction in cholesterol, markedly reduced plasma phospholipids, and an almost complete lack of high density lipoproteins (HDL) when compared with wild-type littermates (+\/+). Fractionation of lipoproteins by FPLC demonstrated dramatic alterations in HDL cholesterol (HDL-C), including the near absence of apolipoprotein AI. Low density lipoprotein (LDL) cholesterol (LDL-C) and apolipoprotein B were also significantly reduced in +\/\u2212 and \u2212\/\u2212 compared with their littermate controls. The inactivation of the\n                    <jats:italic>Abc1<\/jats:italic>\n                    gene led to an increase in the absorption of cholesterol in mice fed a chow or a high-fat and -cholesterol diet. Histopathologic examination of\n                    <jats:italic>Abc1<\/jats:italic>\n                    \u2212\/\u2212 mice at ages 7, 12, and 18 mo demonstrated a striking accumulation of lipid-laden macrophages and type II pneumocytes in the lungs. Taken together, these findings demonstrate that\n                    <jats:italic>Abc1<\/jats:italic>\n                    \u2212\/\u2212 mice display pathophysiologic hallmarks similar to human Tangier disease and highlight the capacity of ABC1 transporters to participate in the regulation of dietary cholesterol absorption.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.8.4245","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"4245-4250","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":465,"title":["High density lipoprotein deficiency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1"],"prefix":"10.1073","volume":"97","author":[{"given":"John","family":"McNeish","sequence":"first","affiliation":[{"name":"Central Research Division, Pfizer Incorporated, Eastern Point Road, Groton, CT 06340; and Centre D'Immunologie, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale-Centre National de la Recherche Scientifique de Marseille\u2013Luminy, Parc Scientific de Luminy, 13288 Marseille, Cedex 9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Aiello","sequence":"additional","affiliation":[{"name":"Central Research Division, Pfizer Incorporated, Eastern Point Road, Groton, CT 06340; and Centre D'Immunologie, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale-Centre National de la Recherche Scientifique de Marseille\u2013Luminy, Parc Scientific de Luminy, 13288 Marseille, Cedex 9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Guyot","sequence":"additional","affiliation":[{"name":"Central Research Division, Pfizer Incorporated, Eastern Point Road, Groton, CT 06340; and Centre D'Immunologie, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale-Centre National de la Recherche Scientifique de Marseille\u2013Luminy, Parc Scientific de Luminy, 13288 Marseille, Cedex 9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Turi","sequence":"additional","affiliation":[{"name":"Central Research Division, Pfizer Incorporated, Eastern Point Road, Groton, CT 06340; and Centre D'Immunologie, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale-Centre National de la Recherche Scientifique de Marseille\u2013Luminy, Parc Scientific de Luminy, 13288 Marseille, Cedex 9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Gabel","sequence":"additional","affiliation":[{"name":"Central Research Division, Pfizer Incorporated, Eastern Point Road, Groton, CT 06340; and Centre D'Immunologie, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale-Centre National de la Recherche Scientifique de Marseille\u2013Luminy, Parc Scientific de Luminy, 13288 Marseille, Cedex 9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Aldinger","sequence":"additional","affiliation":[{"name":"Central Research Division, Pfizer Incorporated, Eastern Point Road, Groton, CT 06340; and Centre D'Immunologie, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale-Centre National de la Recherche Scientifique de Marseille\u2013Luminy, Parc Scientific de Luminy, 13288 Marseille, Cedex 9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Central Research Division, Pfizer Incorporated, Eastern Point Road, Groton, CT 06340; and Centre D'Immunologie, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale-Centre National de la Recherche Scientifique de Marseille\u2013Luminy, Parc Scientific de Luminy, 13288 Marseille, Cedex 9, 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