{"entity": "publication", "iuid": "67fe70a7254545e7b2be4a509f5ff479", "timestamp": "2026-06-18T14:38:18.999Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/67fe70a7254545e7b2be4a509f5ff479.json"}, "display": {"href": "https://publications.scilifelab.se/publication/67fe70a7254545e7b2be4a509f5ff479"}}, "title": "Functionally characterizing obesity-susceptibility genes using CRISPR/Cas9, in vivo imaging and deep learning.", "authors": [{"family": "Mazzaferro", "given": "Eugenia", "initials": "E"}, {"family": "Mujica", "given": "Endrina", "initials": "E"}, {"family": "Zhang", "given": "Hanqing", "initials": "H"}, {"family": "Emmanouilidou", "given": "Anastasia", "initials": "A"}, {"family": "Jenseit", "given": "Anne", "initials": "A"}, {"family": "Evcimen", "given": "Bade", "initials": "B"}, {"family": "Metzendorf", "given": "Christoph", "initials": "C"}, {"family": "Dethlefsen", "given": "Olga", "initials": "O"}, {"family": "Loos", "given": "Ruth Jf", "initials": "RJ"}, {"family": "Vienberg", "given": "Sara Gry", "initials": "SG"}, {"family": "Larsson", "given": "Anders", "initials": "A"}, {"family": "Allalou", "given": "Amin", "initials": "A"}, {"family": "den Hoed", "given": "Marcel", "initials": "M"}], "type": "journal article", "published": "2025-02-13", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "15", "issue": "1", "pages": "5408"}, "abstract": "Hundreds of loci have been robustly associated with obesity-related traits, but functional characterization of candidate genes remains a bottleneck. Aiming to systematically characterize candidate genes for a role in accumulation of lipids in adipocytes and other cardiometabolic traits, we developed a pipeline using CRISPR/Cas9, non-invasive, semi-automated fluorescence imaging and deep learning-based image analysis in live zebrafish larvae. Results from a dietary intervention show that 5 days of overfeeding is sufficient to increase the odds of lipid accumulation in adipocytes by 10 days post-fertilization (dpf, n = 275). However, subsequent experiments show that across 12 to 16 established obesity genes, 10 dpf is too early to detect an effect of CRISPR/Cas9-induced mutations on lipid accumulation in adipocytes (n = 1014), and effects on food intake at 8 dpf (n = 1127) are inconsistent with earlier results from mammals. Despite this, we observe effects of CRISPR/Cas9-induced mutations on ectopic accumulation of lipids in the vasculature (sh2b1 and sim1b) and liver (bdnf); as well as on body size (pcsk1, pomca, irs1); whole-body LDLc and/or total cholesterol content (irs2b and sh2b1); and pancreatic beta cell traits and/or glucose content (pcsk1, pomca, and sim1a). Taken together, our results illustrate that CRISPR/Cas9- and image-based experiments in zebrafish larvae can highlight direct effects of obesity genes on cardiometabolic traits, unconfounded by their - not yet apparent - effect on excess adiposity.", "doi": "10.1038/s41598-025-89823-2", "pmid": "39948378", "labels": {"NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics (NBIS)": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11825957"}, {"db": "pii", "key": "10.1038/s41598-025-89823-2"}], "notes": [], "created": "2025-09-08T11:37:27.351Z", "modified": "2025-11-28T10:47:20.122Z"}