Uncovering Variation in Zebrafish: mRNA Expression Profiles By Sex and Strain

Understanding variation in model systems is critical for applying laboratory-based evidence to the real-world. Zebrafish (Danio rerio) are a popular model system, but little is known about existing phenotypic differences between laboratory strains. Commonly used strains possess significant genomic divergence, so we tested whether strains exhibit differences in baseline mRNA expression. Using Agilent 4x44K mRNA expression arrays, we compared hepatic total mRNA expression in adult AB, TU, and WIK (n=3/sex/strain) zebrafish. Arrays were standardized using normalized expression and cyclic Loess correction. Pairwise comparisons between strains produced a list of 124 genes showing ≥ 2-fold increase in mRNA expression between the sexes in at least one strain (q < 0.01). Across strains, 52 genes are highly expressed in males and 72 are highly expressed in females. 57 genes in AB, 4 in TU, and 15 in WIK were uniquely expressed between sexes. PANTHER molecular functional analysis associates these genes with catalytic (29.3%) or binding activity (22.8%). A single gene was identified to be differentially regulated in both males and females across strains. Endoplasmic reticulum lectin 1 (erlec1) is expressed equally between the sexes in TU, but is 3.36-fold higher in male WIK vs female and 2.88-fold higher in female AB vs male. erlec1 is highly conserved, involved in stress-response pathways, and has documented genomic copy number variation in humans. The variation we uncovered in mRNA expression across sexes and strains should be exploited in the zebrafish model system as an accurate representation of the existing variation in natural populations.