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Using a combination of molecular techniques, we studied\n                    <jats:italic>Abca4<\/jats:italic>\n                    knockout (simulating human noncoding disease variants) and\n                    <jats:italic>Abca4<\/jats:italic>\n                    knock-in mice (simulating human misfolded, catalytically inactive protein variants), which serve as models for Stargardt-1 disease. We compared the two strains to ascertain whether they exhibit differential responses to agents that affect cytokine signaling and\/or ceramide metabolism, as alterations in either of these pathways can exacerbate retinal degenerative phenotypes. We found different degrees of responsiveness to maraviroc, a known immunomodulatory CCR5 antagonist, and to the ceramide-lowering agent AdipoRon, an agonist of the ADIPOR1 and ADIPOR2 receptors. The two strains also display different degrees of transcriptional deviation from matched WT controls. Our phenotypic comparison of the two distinct\n                    <jats:italic>Abca4<\/jats:italic>\n                    mutant-mouse models sheds light on potential therapeutic avenues previously unexplored in the treatment of Stargardt disease and provides a surrogate assay for assessing the effectiveness for genome editing.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2314698120","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T13:41:15Z","timestamp":1702042875000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["Distinct mouse models of Stargardt disease display differences in pharmacological targeting of ceramides and inflammatory responses"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5411-456X","authenticated-orcid":false,"given":"Zachary J.","family":"Engfer","sequence":"first","affiliation":[{"name":"Gavin Herbert Eye 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