New mouse models with hypomorphic SUMF1 variants mimic attenuated forms of multiple sulfatase deficiency.

Document Type


Publication Date



JMG, SS1, Humans, Animals, Mice, Multiple Sulfatase Deficiency Disease, Mutation, Sulfatases, Mutation, Missense, Lysosomal Storage Diseases, Oxidoreductases Acting on Sulfur Group Donors








We acknowledge financial support from MSD Action Foundation/Saving Dylan.com to NBP and Nicolina Cristina Sorrentino, and MSD-Action Foundation/Saving Dylan.com to Cathleen Lutz. NIH fund- ing to Cathleen Lutz, NIH U42OD010921; Mutant Mouse Resource and Research Center (MMRRC) at The Jackson Laboratory.


Multiple sulfatase deficiency (MSD) is an ultrarare lysosomal storage disorder due to deficiency of all known sulfatases. MSD is caused by mutations in the Sulfatase Modifying Factor 1 (SUMF1) gene encoding the enzyme responsible for the post-translational modification and activation of all sulfatases. Most MSD patients carry hypomorph SUMF1 variants resulting in variable degrees of residual sulfatase activities. In contrast, Sumf1 null mice with complete deficiency in all sulfatase enzyme activities, have very short lifespan with significant pre-wean lethality, owing to a challenging preclinical model. To overcome this limitation, we genetically engineered and characterized in mice two commonly identified patient-based SUMF1 pathogenic variants, namely p.Ser153Pro and p.Ala277Val. These pathogenic missense variants correspond to variants detected in patients with attenuated MSD presenting with partial-enzyme deficiency and relatively less severe disease. These novel MSD mouse models have a longer lifespan and show biochemical and pathological abnormalities observed in humans. In conclusion, mice harboring the p.Ser153Pro or the p.Ala277Val variant mimic the attenuated MSD and are attractive preclinical models for investigation of pathogenesis and treatments for MSD.

Please contact the Joan Staats Library for information regarding this document.