Iron supplementation in zebrafish models of mucopolysaccharidoses type III

Sanfilippo Syndrome Type B, characterized by a deficiency in N-acetylglucosaminidase (NAGLU) enzyme, represents a debilitating genetic disorder which causes childhood dementia. In this study, we employed zebrafish models carrying the naglu A603fs mutation to investigate the potential of intraperitoneal (i.p.) injection of ferric citrate to rescue whole brain transcriptomes relative to an i.p. injection of saline vehicle control. Zebrafish, aged 6 months, were either homozygous (MPS IIIB) and heterozygous (unaffected control) genotypes, and each group was subjected to either ferric citrate or saline injection. A total of 10 fish per genotype and treatment were examined via RNA-seq. Although initial findings identified sex-specific differences in inflammation pathways and regeneration which may be rescued in female samples (but not in males), the sample size of fish per genotype, sex, and treatment limited the ability to draw definitive conclusions. Whole-brain profiles from heterozygous (naglu A603fs/+, unaffected control) and homozygous mutant siblings (naglu A603fs/A603fs, MPS IIIB) zebrafish 7 days after an i.p. injection of ferric citrate (10 micrograms) or 0.85% saline control. Brains were taken from zebrafish aged at 6 months.