Lysosomal storage diseases (LSDs) are a family of 70 metabolic disorders characterized by mutations in lysosomal proteins that lead to storage material accumulation, multipleorgan pathologies that often involve neurodegeneration, and early mortality in a significant number of patients. Along with the necessity for more effective therapies, there exists an unmet need for further understanding of disease etiology, which could uncover novel pathways and drug targets. Over the past few decades, the growth in knowledge of disease-associated pathways has been facilitated by studies in model organisms, as advancements in mutagenesis techniques markedly improved the efficiency of model generation in mammalian and non-mammalian systems. In this review we highlight non-mammalian models of LSDs, focusing specifically on the zebrafish, a vertebrate model organism that shares remarkable genetic and metabolic similarities with mammals while also conferring unique advantages such as optical transparency and amenability toward high-throughput applications. We examine published zebrafish LSD models and their reported phenotypes, address organismspecific advantages and limitations, and discuss recent technological innovations that could provide potential solutions.

ABSTRACT. Hepatitis B virus (HBV) infection can cause HBVrelated cirrhosis, liver failure, and hepatocellular carcinoma. At present, a hepatitis B surface antigen (HBsAg) blood test is the primary clinical and diagnostic marker for the identification of a chronic HBV infection. In the current study, we isolated a novel HBV mutant from a chronic HBV patient, capable of causing a false negative test result for most (7 of 8) commercial HBsAg ELISA kits. DNA sequencing of the HBsAg region of this HBV mutant revealed two novel mutation sites that resulted in a Thr-to-Met substitution at amino acid (aa) position 118 and a Lys to Asn substitution at aa position 122 of HBsAg. Moreover, a mutagenesis assay showed that the aa118 (Thr to Met) mutation was the leading cause of the false negative results from the HBsAg ELISA tests. The false negative result was restored, in that the mutation was correctly detected, when the Thr at aa position 118 of this mutated HBsAg was reconstituted. In conclusion, our study revealed a novel aa118 Met mutation of HBsAg HBV that will benefit the future development of HBV diagnosis.