3 research outputs found

    Lafora Disease Is an Inherited Metabolic Cardiomyopathy

    Get PDF
    This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2015-65722-R to Dr. Lara-Pezzi and SAF2014-59594-R to Dr. Serratosa), Autonomous Community of Madrid (2010-BMD2321, FIBROTEAM Consortium), European Union's FP7 (CardioNeT-ITN-289600, CardioNext-ITN-608027), the Spanish Carlos III Institute of Health (CPII14/00027 to Dr. Lara-Pezzi, PI13/00865 to Dr. Sanchez and RD12/0042/066 to Drs. Garcia-Pavia and Lara-Pezzi), and the National Institute of Neurological Disorders And Stroke of the National Institutes of Health (P01NS097197 to Dr. Sanchez). This work was also supported by the Plan Estatal de I+D+I 2013-2016-European Regional Development Fund (FEDER) "A way of making Europe," Spain. The Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).S

    Unexpected Phenotype Reversion and Survival in a Zebrafish Model of Multiple Sulfatase Deficiency.

    No full text
    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 SUMF1 gene, which encodes the formylglycine-generating enzyme (FGE), and responsible for the activation of sulfatases. Mutations in SUMF1 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 sumf1 null zebrafish model, which has negligible sulfatase activity. Our sumf1 -/- 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 Sumf1 -/- 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 sumf1 -/- null zebrafish to survive better than human MSD patients and mouse Sumf1 -/- models
    corecore