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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.
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This content will become publicly available on February 1, 2026
Genetics of Physiological Variation Within and Between Larval Wild-Type AB and Backcrossed NHGRI-1 Zebrafish (Danio rerio)
Changes in the environment promote variations in fish physiological responses. Genetic variation also plays a role in physiological variation. To explore the role of genetics in physiological variation, we assessed variation of cardiac function (heart rate, stroke volume, and cardiac output), oxygen consumption, yolk conversion efficiency, and cost of development in embryonic and larval AB wild-type and NHGRI-1 zebrafish (low heterozygosity line backcrossed from AB wild-type) exposed to different temperature and oxygen regimes. Fish were exposed from fertilization to 7 days post-fertilization (dpf) to control conditions (28 °C, 21% O2) or to low temperature (23 °C, 21% O2), high temperature (33 °C, 21% O2), moderate hypoxia (28 °C, 13% O2), or severe hypoxia (28 °C, 10% O2). We hypothesized that (1) assessed physiological variables will respond similarly in both fish lines and (2) data variability in the low heterozygosity NHGRI-1 zebrafish will be lower than in AB zebrafish. Cardiac function decreased at lower temperature and in hypoxia in both AB and NHGRI-1 zebrafish. Oxygen consumption was increased by higher temperature and hypoxia in AB fish and by severe hypoxia in NHGRI-1 fish. Yolk conversion efficiency was decreased by lower temperature and hypoxia in AB fish and increased by higher temperature and decreased by hypoxia in NHGRI-1 fish. Cost of development was higher mainly in hypoxia-treated fish. Supporting our hypothesis that genetics contributes to physiological variation, NHGRI-1 zebrafish data showed significantly lower coefficients of variation in 84% of assessed endpoints. We conclude that (1) there is a strong genetic component to physiological variation in fishes and (2) low heterozygosity NHGRI-1 zebrafish are useful models for reducing the ‘noise’ from genetic backgrounds in physiological research in fish, which may aid interpretation of experimental results and facilitate reproducibility.
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- Award ID(s):
- 2103499
- PAR ID:
- 10585648
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- Fishes
- Volume:
- 10
- Issue:
- 2
- ISSN:
- 2410-3888
- Page Range / eLocation ID:
- 59
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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