Genetic Basis for Morphological Variation in the Zebrafish Danio rerio: Insights from a Low-Heterozygosity Line

Data variability complicates reproducibility and the interpretation of experimental results. Different animal models have been employed to decrease variability to enhance experimental power. However, variation frequently persists among and within strains/lines. In zebrafish (Danio rerio), inbred lines (e.g., NHGRI-1) derived from wild-type lines have been produced to greatly decrease genetic variation, with the goal of providing better understanding of genetic backgrounds that may influence the experimental outcome of studies employing such lines. We hypothesized that variations in morphological phenotypes shaped by environmental stressors early in development are correlated with the intrinsic degree of genetic variability of zebrafish lines. We compared morphological variability (yolk-chorion ratio, body mass, embryo mass, total length, condition factor, and specific growth rate) in wild-type AB and NHGRI-1 zebrafish lines as a function of their responses to altered temperature and oxygen availability during the first 7 days post-fertilization. Overall, both lines showed similar developmental trajectories for yolk-chorion ratio, embryo mass, and total length. Additionally, condition factor and specific growth rate showed similar responses within each line, regardless of temperature and hypoxia. Importantly, the coefficient of variation for each variable was significantly lower in NHGRI-1 than AB larvae for 151 of 187 assessed morphological endpoints. Thus, the low-heterozygosity NHGRI-1 zebrafish line can be useful for decreasing inter-individual variation in morphological responses to environmental stressors, thereby aiding in the interpretation of results and enhancing experimental reproducibility.