Transcriptomic profiling of zebrafish mutants for orthologs of genes that increase schizophrenia risk

In this study, we used CRISPR/Cas9 to knock out multiple orthologs of genes that increase risk for schizophrenia in humans. Gene sets included those from SCHEMA (exome sequencing), copy number variatns, and de novo mutations in childhood onset schizophrenia. Larval brain activity and behavior as assessed for all lines. The truncating sp4 and atp1a3a-v139m point mutation were selected for transcriptomic analysis. Overall design: RNA-sequencing of dissected heads of larval zebrafish and dissected whole brains from adults. Two heterozygous parents were crossed together, and larvae from one clutch were dissected at 6 days post-fertilization or animals were grown until adulthood until dissection. Mutant and wild-type control sibling embryos were identified by genotyping after dissection for larvae, and 3-5 heads were pooled for each biological replicate. Genotypes of adults were identified by finclipping prior to dissection. At least five biological replicates were collected per genotype.