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Cell Dev. Biol."],"abstract":"<jats:p>Multiple sulfatase deficiency (MSD) is a rare recessively inherited Mendelian disorder that manifests with developmental delay, neurodegeneration, skeletal deformities, facial dysmorphism, congenital growth retardation, and other clinical signs. The disorder is caused by mutations in the <jats:italic>SUMF1<\/jats:italic> gene, which encodes the formylglycine-generating enzyme (FGE), and responsible for the activation of sulfatases. Mutations in <jats:italic>SUMF1<\/jats:italic> result in reduced or absent FGE function with consequent compromised activities of its client sulfatases. This leads to an accumulation of enzyme substrates, such as glycosaminoglycans and sulfolipids, within lysosomes and subsequently impaired lysosome function and cellular pathology. Currently, there are no disease modifying therapeutic options for MSD patients, hence the need for more suitable animal models to investigate the disorder. Here, we describe the characterisation of a <jats:italic>sumf1<\/jats:italic> null zebrafish model, which has negligible sulfatase activity. Our <jats:italic>sumf1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> zebrafish model successfully recapitulates the pathology of MSD such as cranial malformation, altered bone development, an enlarged population of microglia, and growth retardation during early development but lacks early lethality of mouse <jats:italic>Sumf1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> models. Notably, we provide evidence of recovery in MSD pathology during later developmental stages, resulting in homozygous mutants that are viable. Hence, our data suggest the possibility of a unique compensatory mechanism that allows the <jats:italic>sumf1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> null zebrafish to survive better than human MSD patients and mouse <jats:italic>Sumf1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> models.<\/jats:p>","DOI":"10.3389\/fcell.2022.843079","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T21:16:29Z","timestamp":1654204589000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Unexpected Phenotype Reversion and Survival in a Zebrafish Model of Multiple Sulfatase Deficiency"],"prefix":"10.3389","volume":"10","author":[{"given":"Angeleen","family":"Fleming","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Low Zhe","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gentzane","family":"Sanchez-Elexpuru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah V.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dylan","family":"Windell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael H.","family":"Gelb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zackary M.","family":"Herbst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Schlotawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Rubinsztein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/bs.mcb.2016.10.001","article-title":"Investigating Microglia-Brain Tumor Cell Interactions In Vivo in the Larval Zebrafish Brain","volume":"138","author":"Astell","year":"2017","journal-title":"Methods Cell Biol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/0009-8981(59)90119-6","article-title":"The Assay of Arylsulphatases A and B in Human Urine","volume":"4","author":"Baum","year":"1959","journal-title":"Clinica Chim. 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