Transcriptomics analysis of a zebrafish model of Combined Saposin Deficiency

Combined Saposin Deficiency is a lysosomal storage disease with multiple-organ pathologies that often involve neurodegeneration and early mortality. To investigate the mechanisms driving saposin loss-associated demyelination, the brains of psap-/- zebrafish and wildtype siblings were analyzed via RNA-seq. A zebrafish model of Combined Saposin Deficiency was generated using CRISPR-Cas9 targeting the prosaposin (psap) gene, which codes for saposins A-D. Mutagenized alleles were identified by DNA fragment analysis and Sanger sequencing, and fish carrying the mutations of interest were propagated to homozygosity. RNA was isolated from the brains of four months-post-fertilization psap-/- zebrafish and wildtype siblings.