{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:23:22Z","timestamp":1787502202860,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Patients affected by the rare disease pseudoxanthoma elasticum (PXE) exhibit the calcification of elastic fibers in ocular, dermal, and vascular tissues. These symptoms are triggered by mutations in the ATP-binding cassette transporter subfamily C member 6 (ABCC6), whose substrate remains unknown. Interestingly, ABCC6 is predominantly expressed in the liver tissue, leading to the hypothesis that PXE is a metabolic disorder. We developed a genome-editing system targeting ABCC6 in human immortalized hepatocytes (HepIms) for further investigations. The HepIms were transfected with an ABCC6-specific clustered regulatory interspaced short palindromic repeat (CRISPR-Cas9) genome-editing plasmid, resulting in the identification of a heterozygous (htABCC6HepIm) and a compound heterozygous (chtABCC6HepIm) clone. These clones were analyzed for key markers associated with the PXE pathobiochemistry. Hints of impaired lipid trafficking, defects in the extracellular matrix remodeling, the induction of calcification inhibitor expression, and the down regulation of senescence and inflammatory markers in ABCC6-deficienct HepIms were found. Our ABCC6 knock-out model of HepIms provides a valuable tool for studying the metabolic characteristics of PXE in vitro. The initial analysis of the clones mirrors various features of the PXE pathobiochemistry and provides an outlook on future research approaches.<\/jats:p>","DOI":"10.3390\/cells14080576","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T10:05:51Z","timestamp":1744365951000},"page":"576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigation on ABCC6-Deficient Human Hepatocytes Generated by CRISPR\u2013Cas9 Genome Editing"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-9415","authenticated-orcid":false,"given":"Ricarda","family":"Pl\u00fcmers","sequence":"first","affiliation":[{"name":"Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, Medizinische Fakult\u00e4t OWL (Universit\u00e4t Bielefeld), Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Jelinek","sequence":"additional","affiliation":[{"name":"Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, Medizinische Fakult\u00e4t OWL (Universit\u00e4t Bielefeld), Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Lindenkamp","sequence":"additional","affiliation":[{"name":"Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, Medizinische Fakult\u00e4t OWL (Universit\u00e4t Bielefeld), Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel R.","family":"Osterhage","sequence":"additional","affiliation":[{"name":"Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, Medizinische Fakult\u00e4t OWL (Universit\u00e4t Bielefeld), Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius","family":"Knabbe","sequence":"additional","affiliation":[{"name":"Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, Medizinische Fakult\u00e4t OWL (Universit\u00e4t Bielefeld), Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3660-6923","authenticated-orcid":false,"given":"Doris","family":"Hendig","sequence":"additional","affiliation":[{"name":"Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, Medizinische Fakult\u00e4t OWL (Universit\u00e4t Bielefeld), Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/cbf.653","article-title":"Proteoglycan alterations in skin fibroblast cultures from patients affected with pseudoxanthoma elasticum","volume":"14","author":"Passi","year":"1996","journal-title":"Cell Biochem. 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