A ZEBRATISH IDURONATE-2-SULFATASE CANDIDATE ORTHOLOGUE IS STRONGLY EXPRESSED DURING EARLY EMBRYONIC DEVELOPMENT

Introduction and hypothesis: Iduronate-2-sulfatase (IDS) is a lysosomal enzyme responsible for the removal of the 2-sulfate group from dermatan and heparan sulfate. The protein plays a key role in the degradation of glycosaminoglycans (GAG) and its deficiency in humans causes the rare X-linked recessive lysosomal storage disorder called Hunter syndrome or mucopolysaccharidosis type II. The importance of glycosaminoglycans in embryonic development is well known; we speculated that also IDS, involved in GAG metabolism, may have a specific developmental role. Methods, results and conclusions: To address this issue we isolated a candidate IDS orthologue in the tropical teleost Danio Rerio (zIDS).Through a bioinformatic and molecular approach we have cloned a 1683 bp sequence coding for a 561aa protein with a 75% homology to human alpha IDS precursor. Blast alignment and protein domain homology suggest a conserved function of the zebrafish orthologue. By whole mount in situ hybridization very high expression levels of zIDS were detected at early developmental stages, thus evoking a maternal origin of the enzyme. High enzymatic activity during this early stage was also confirmed using the fluorogenic 4-methylumbelliferyl-α-iduronide-2-sulfate substrate based assay. Later, transcripts were detected in the brain, vascular mesenchyme and splanchnocranium cartilage, supporting a key role of the zebrafish IDS during development. Current investigations are focused to knock-down the expression of the gene using the morpholino technology.