{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T07:27:18Z","timestamp":1762327638413,"version":"build-2065373602"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>\n                    Zellweger spectrum disorders (ZSDs) are rare autosomal recessive conditions belonging to the larger group of peroxisome biogenesis disorders. The most prevalent form of ZSD is caused by mutations in the\n                    <jats:italic>PEX1<\/jats:italic>\n                    gene, which encodes an AAA ATPase protein. Cells lacking functional PEX1 fail to import proteins crucial for the formation of competent peroxisomes, resulting in aberrant structures called\n                    <jats:italic>ghost peroxisomes<\/jats:italic>\n                    . Peroxisome dysfunction leads to the accumulation of compounds that are normally metabolized in this compartment, including very long-chain fatty acids (VLCFAs), pristanic and phytanic acids, as well as deficiency in compounds that are normally formed in this organelle, including docosahexaenoic acid (DHA) and plasmalogen precursors. Patients with a complete lack of PEX1 function develop severe symptoms and have a poor prognosis, with death in the first year of life. In the absence of effective treatments for ZSD, advancing our understanding of this complex multisystem disorder remains essential for uncovering new therapeutic opportunities. To this end, we generated and characterized a zebrafish model with Pex1 loss-of-function. Surprisingly, despite the early onset of disease-relevant features, about 10% of\n                    <jats:italic>pex1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    zebrafish reached adulthood. However, this resilience was short-lived, as none of the mutant fish survived beyond one year. Histopathological analysis of the liver in adult\n                    <jats:italic>pex1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mutants revealed a profound peroxisomal import deficiency and severe vacuolation. Moreover, key metabolic hallmarks of ZSDs, including accumulation of VLCFAs and methyl-branched fatty acids phytanic and pristanic acid, were consistently detected in larval and adult\n                    <jats:italic>pex1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mutants. Transcriptomics analysis in\n                    <jats:italic>pex1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    larvae revealed upregulation of ER-stress responses and pexophagy, as well as dysregulation of neurophysiological processes and visual perception. The latter findings were corroborated by abnormal locomotor behavior in the larvae and by disrupted outer nuclear and retinal layer architecture in adult mutant animals. The described zebrafish\n                    <jats:italic>pex1<\/jats:italic>\n                    model provides a versatile\n                    <jats:italic>in vivo<\/jats:italic>\n                    platform to uncover novel disease-relevant pathways in ZSD and to investigate the physiological impact of VLCFAs and methyl-branched fatty acids. Its relative tolerance to Pex1 loss-of-function circumvents the early lethality observed in mouse models, enabling the study of ZSD pathophysiology beyond early developmental stages and offering a valuable tool for preclinical therapeutic exploration.\n                  <\/jats:p>","DOI":"10.3389\/fnmol.2025.1634536","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:29:11Z","timestamp":1762324151000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pex1 loss-of-function in zebrafish is viable and recapitulates hallmarks of Zellweger spectrum disorders"],"prefix":"10.3389","volume":"18","author":[{"given":"Ursula","family":"Heins-Marroquin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zlatan","family":"Hodzic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz Soares Carneiro","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnes","family":"Hendriks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floriane","family":"Gavotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc O.","family":"Warmoes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Schlicker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samy","family":"Omri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"J\u00e4ger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Glaab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy E.","family":"Braverman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Lorena","family":"Cordero-Maldonado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole L.","family":"Linster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1177\/0023677219869037","article-title":"Zebrafish: Housing and husbandry recommendations.","volume":"54","author":"Alestr\u00f6m","year":"2020","journal-title":"Lab. Anim."},{"key":"B2","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1186\/s13023-021-01940-z","article-title":"Cholbam\u00ae and Zellweger spectrum disorders: Treatment implementation and management.","volume":"16","author":"Anderson","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"107713","DOI":"10.1016\/j.exer.2019.107713","article-title":"A longitudinal study of retinopathy in the PEX1-Gly844Asp mouse model for mild Zellweger spectrum disorder.","volume":"186","author":"Argyriou","year":"2019","journal-title":"Exp. Eye Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.omtm.2021.09.002","article-title":"AAV-mediated PEX1 gene augmentation improves visual function in the PEX1-Gly844Asp mouse model for mild Zellweger spectrum disorder.","volume":"23","author":"Argyriou","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/ng0997-49","article-title":"A mouse model for Zellweger syndrome.","volume":"17","author":"Baes","year":"1997","journal-title":"Nat. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing.","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s00018-023-04700-3","article-title":"Loss of pex5 sensitizes zebrafish to fasting due to deregulated mitochondria, mTOR, and autophagy.","volume":"80","author":"Bhandari","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1111\/j.1574-6976.2011.00267.x","article-title":"Phosphoethanolamine methyltransferases in phosphocholine biosynthesis: Functions and potential for antiparasite therapy.","volume":"35","author":"Bobenchik","year":"2011","journal-title":"FEMS Microbiol. Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/ddrr.1113","article-title":"Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives.","volume":"17","author":"Braverman","year":"2013","journal-title":"Dev. Disabil. Res. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1242\/jeb.003939","article-title":"Modulation of locomotor activity in larval zebrafish during light adaptation.","volume":"210","author":"Burgess","year":"2007","journal-title":"J. Exp. Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/humu.20211","article-title":"PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders.","volume":"26","author":"Crane","year":"2005","journal-title":"Hum. Mutat."},{"key":"B12","doi-asserted-by":"publisher","first-page":"165900","DOI":"10.1016\/j.bbadis.2020.165900","article-title":"Longitudinal study of Pex1-G844D NMRI mouse model: A robust pre-clinical model for mild Zellweger spectrum disorder.","volume":"1866","author":"Demaret","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1080\/15548627.2022.2160566","article-title":"PEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS.","volume":"19","author":"Demers","year":"2023","journal-title":"Autophagy"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1101\/gr.215954.116","article-title":"Dynamic RNA\u2013protein interactions underlie the zebrafish maternal-to-zygotic transition.","volume":"27","author":"Despic","year":"2017","journal-title":"Genome Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1126\/science.1181498","article-title":"Human genome sequencing using unchained base reads on self-assembling DNA Nanoarrays.","volume":"327","author":"Drmanac","year":"2010","journal-title":"Science"},{"key":"B16","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1002\/humu.21388","article-title":"Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder.","volume":"32","author":"Ebberink","year":"2011","journal-title":"Hum. Mutat."},{"key":"B17","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1083\/jcb.200311131","article-title":"PEX3 functions as a PEX19 docking factor in the import of class I peroxisomal membrane proteins.","volume":"164","author":"Fang","year":"2004","journal-title":"J. Cell Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1385\/JMN:16:2-3:289","article-title":"The peroxisome deficient PEX2 Zellweger mouse: Pathologic and biochemical correlates of lipid dysfunction.","volume":"16","author":"Faust","year":"2001","journal-title":"J. Mol. Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.ymgme.2008.11.165","article-title":"Toxicity of peroxisomal C27-bile acid intermediates.","volume":"96","author":"Ferdinandusse","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1016\/S0022-2275(20)31527-3","article-title":"Identification of the peroxisomal \u03b2-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid.","volume":"42","author":"Ferdinandusse","year":"2001","journal-title":"J. Lipid Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e98186","DOI":"10.1371\/journal.pone.0098186","article-title":"Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs.","volume":"9","author":"Gagnon","year":"2014","journal-title":"PLoS One"},{"key":"B22","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41467-017-02474-4","article-title":"The peroxisomal AAA-ATPase Pex1\/Pex6 unfolds substrates by processive threading.","volume":"9","author":"Gardner","year":"2018","journal-title":"Nat. Commun."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1016\/j.jmb.2015.01.019","article-title":"The Pex1\/Pex6 complex is a heterohexameric AAA + Motor with alternating and highly coordinated subunits.","volume":"427","author":"Gardner","year":"2015","journal-title":"J. Mol. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e202302057","DOI":"10.26508\/lsa.202302057","article-title":"CLN3 deficiency leads to neurological and metabolic perturbations during early development.","volume":"7","author":"Heins-Marroquin","year":"2024","journal-title":"Life Sci. Alliance"},{"key":"B25","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1016\/j.ymgme.2014.01.008","article-title":"The Pex1-G844D mouse: A model for mild human Zellweger spectrum disorder.","volume":"111","author":"Hiebler","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"B26","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1194\/jlr.R000042","article-title":"Bile salts of vertebrates: Structural variation and possible evolutionary significance.","volume":"51","author":"Hofmann","year":"2010","journal-title":"J. Lipid Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s13023-015-0368-9","article-title":"Zellweger spectrum disorders: Clinical overview and management approach.","volume":"10","author":"Klouwer","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.bbalip.2012.02.011","article-title":"Peroxisome deficiency-induced ER stress and SREBP-2 pathway activation in the liver of newborn PEX2 knock-out mice.","volume":"1821","author":"Kovacs","year":"2012","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"B29","first-page":"102","article-title":"Pharmacological ER stress promotes hepatic lipogenesis and lipid droplet formation.","volume":"4","author":"Lee","year":"2012","journal-title":"Am. J. Transl. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"4358","DOI":"10.1128\/MCB.22.12.4358-4365.2002","article-title":"PEX11\u03b2 deficiency is lethal and impairs neuronal migration but does not abrogate peroxisome function.","volume":"22","author":"Li","year":"2002","journal-title":"Mol. Cell Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkz114","article-title":"The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads.","volume":"47","author":"Liao","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/S0896-6273(00)80783-7","article-title":"Laser ablations reveal functional relationships of segmental hindbrain neurons in Zebrafish.","volume":"23","author":"Liu","year":"1999","journal-title":"Neuron"},{"key":"B33","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method.","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B34","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1126\/science.284.5418.1362","article-title":"Identification of a nuclear receptor for bile acids.","volume":"284","author":"Makishima","year":"1999","journal-title":"Science"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1212\/WNL.40.8.1292","article-title":"Severe deficiency of docosahexaenoic acid in peroxisomal disorders.","volume":"40","author":"Mart\u00ednez","year":"1990","journal-title":"Neurology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"7067","DOI":"10.1007\/BF02637067","article-title":"Docosahexaenoic acid therapy in docosahexaenoic acid-deficient patients with disorders of peroxisomal biogenesis.","volume":"31","author":"Martinez","year":"1996","journal-title":"Lipids"},{"key":"B38","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/s41556-024-01364-4","article-title":"Lipid droplets and cellular lipid flux.","volume":"26","author":"Mathiowetz","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3982","DOI":"10.3390\/cells11243982","article-title":"Loss of Pex1 in inner ear hair cells contributes to cochlear synaptopathy and hearing loss.","volume":"11","author":"Mauriac","year":"2022","journal-title":"Cells"},{"key":"B40","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1016\/j.bbalip.2017.06.004","article-title":"Phytol-induced pathology in 2-hydroxyacyl-CoA lyase (HACL1) deficient mice. Evidence for a second non-HACL1-related lyase.","volume":"1862","author":"Mezzar","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1001\/jama.296.15.1885","article-title":"Fish intake, contaminants, and human health.","volume":"296","author":"Mozaffarian","year":"2006","journal-title":"JAMA"},{"key":"B42","doi-asserted-by":"publisher","first-page":"3889","DOI":"10.1038\/s41598-017-04288-2","article-title":"Two alternative pathways for docosahexaenoic acid (DHA, 22:6n-3) biosynthesis are widespread among teleost fish.","volume":"7","author":"Oboh","year":"2017","journal-title":"Sci. Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e55896","DOI":"10.7554\/eLife.55896","article-title":"The peroxisome counteracts oxidative stresses by suppressing catalase import via Pex14 phosphorylation.","volume":"9","author":"Okumoto","year":"2020","journal-title":"Elife"},{"key":"B44","doi-asserted-by":"publisher","first-page":"100771","DOI":"10.1016\/j.jlr.2025.100771","article-title":"Spatial characterization of RPE structure and lipids in the PEX1-p.Gly844Asp mouse model for Zellweger spectrum disorder.","volume":"66","author":"Omri","year":"2025","journal-title":"J. Lipid Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1212\/WNL.0b013e3181f07061","article-title":"Docosahexaenoic acid therapy in peroxisomal diseases.","volume":"75","author":"Paker","year":"2010","journal-title":"Neurology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"E28","DOI":"10.1152\/ajpendo.90897.2008","article-title":"Biochemical and physiological function of stearoyl-CoA desaturase.","volume":"297","author":"Paton","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B47","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1042\/bj2530645","article-title":"The occurrence of polyenoic very long chain fatty acids with greater than 32 carbon atoms in molecular species of phosphatidylcholine in normal and peroxisome-deficient (Zellweger\u2019s syndrome) brain.","volume":"253","author":"Poulos","year":"1988","journal-title":"Biochem. J."},{"key":"B48","year":"2018","journal-title":"R: A language and environment for statistical computing."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2500","DOI":"10.1172\/JCI142500","article-title":"Metabolic rerouting via SCD1 induction impacts X-linked adrenoleukodystrophy.","volume":"131","author":"Raas","year":"2021","journal-title":"J. Clin. Invest."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1194\/jlr.M800138-JLR200","article-title":"Evolution of the bile salt nuclear receptor FXR in vertebrates.","volume":"49","author":"Reschly","year":"2008","journal-title":"J. Lipid Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A bioconductor package for differential expression analysis of digital gene expression data.","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"B52","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1203\/00006450-198509000-00013","article-title":"The Cerebrohepatorenal (Zellweger) syndrome: An improved method for the biochemical diagnosis and its potential value for prenatal detection.","volume":"19","author":"Roscher","year":"1985","journal-title":"Pediatr. Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"129","DOI":"10.12717\/DR.2024.28.4.129","article-title":"Zebrafish PEX1 Is required for the generation of GABAergic neuron in p3 domain.","volume":"28","author":"Ryu","year":"2024","journal-title":"Dev. Reprod."},{"key":"B54","doi-asserted-by":"publisher","first-page":"7809","DOI":"10.1038\/s41598-018-24119-2","article-title":"Super-resolution imaging reveals the sub-diffraction phenotype of Zellweger Syndrome ghosts and wild-type peroxisomes.","volume":"8","author":"Soliman","year":"2018","journal-title":"Sci. Rep."},{"key":"B55","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1093\/nar\/gkg027","article-title":"The zebrafish information network (ZFIN): The zebrafish model organism database.","volume":"31","author":"Sprague","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"3600","DOI":"10.1093\/hmg\/ddx249","article-title":"A zebrafish model of X-linked adrenoleukodystrophy recapitulates key disease features and demonstrates a developmental requirement for abcd1 in oligodendrocyte patterning and myelination.","volume":"26","author":"Strachan","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"B57","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.ymgme.2021.05.002","article-title":"Zebrafish model of human Zellweger syndrome reveals organ-specific accumulation of distinct fatty acid species and widespread gene expression changes.","volume":"133","author":"Takashima","year":"2021","journal-title":"Mol. Genet. Metab."},{"key":"B58","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.ymgme.2016.12.013","article-title":"Detection of unusual very-long-chain fatty acid and ether lipid derivatives in the fibroblasts and plasma of patients with peroxisomal diseases using liquid chromatography-mass spectrometry.","volume":"120","author":"Takashima","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1080\/15548627.2017.1319544","article-title":"The constitutive lipid droplet protein PLIN2 regulates autophagy in liver.","volume":"13","author":"Tsai","year":"2017","journal-title":"Autophagy"},{"key":"B60","doi-asserted-by":"publisher","first-page":"e46400","DOI":"10.1371\/journal.pone.0046400","article-title":"N-3 long-chain polyunsaturated fatty acid supplementation significantly reduces liver oxidative stress in high fat induced steatosis.","volume":"7","author":"Valenzuela","year":"2012","journal-title":"PLoS One"},{"key":"B61","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/0009-8981(87)90428-1","article-title":"Peroxisomal very long-chain fatty acid \u03b2-oxidation in human skin fibroblasts: Activity in Zellweger syndrome and other peroxisomal disorders.","volume":"166","author":"Wanders","year":"1987","journal-title":"Clin. Chim. Acta"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1038\/gim.2017.262","article-title":"A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers.","volume":"20","author":"Wangler","year":"2018","journal-title":"Genet. Med."},{"key":"B63","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1016\/j.bbamcr.2015.11.015","article-title":"Human disorders of peroxisome metabolism and biogenesis.","volume":"1863","author":"Waterham","year":"2016","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"abg1371","DOI":"10.1126\/sciadv.abg1371","article-title":"Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine.","volume":"7","author":"Wen","year":"2021","journal-title":"Sci. Adv."},{"key":"B65","author":"Westerfield","year":"2000","journal-title":"The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio)"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1016\/j.ophtha.2023.07.026","article-title":"Zellweger spectrum disorder: Ophthalmic findings from a new natural history study cohort and scoping literature review.","volume":"130","author":"Yergeau","year":"2023","journal-title":"Ophthalmology"},{"key":"B67","doi-asserted-by":"publisher","first-page":"108897","DOI":"10.1016\/j.jnutbio.2021.108897","article-title":"Visualization of dietary docosahexaenoic acid in whole-body zebrafish using matrix-assisted laser desorption\/ionization mass spectrometry imaging.","volume":"100","author":"Yoshinaga","year":"2022","journal-title":"J. Nutr. Biochem."},{"key":"B68","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters.","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B69","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1089\/zeb.2019.1796","article-title":"Rapid and efficient live Zebrafish embryo genotyping.","volume":"17","author":"Zhang","year":"2020","journal-title":"Zebrafish"}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2025.1634536\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:29:12Z","timestamp":1762324152000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2025.1634536\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,5]]},"references-count":69,"alternative-id":["10.3389\/fnmol.2025.1634536"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2025.1634536","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,5]]},"article-number":"1634536"}}