A fish is not a mouse: understanding differences in background genetics is critical for reproducibility

Area of Science:

• Biomedical research
• Model organism development
• Genetics and genomics

Background:

• Reproducibility crisis in biomedical research linked to uncontrolled animal model genetics.
• Zebrafish (Danio rerio) lack standardized inbred strains or well-characterized outbred stocks.
• Inconsistent breeding practices and poorly defined genetic backgrounds of wild-type zebrafish lines.

Purpose of the Study:

• To highlight the impact of poorly controlled zebrafish background genetics on research reproducibility.
• To propose standardized terminology and detailed reporting of zebrafish genetic origins.
• To advocate for genetic monitoring to ensure zebrafish line integrity and consistency.

Main Methods:

• Historical analysis of the widely used AB zebrafish line's genetic background.
• Review of current practices in zebrafish husbandry and genetic characterization.
• Discussion of the implications of genetic background variability on experimental outcomes.

Main Results:

• Zebrafish wild-type lines, exemplified by the AB line, exhibit dynamic and often uncharacterized genetic complexity.
• Inconsistent genetic backgrounds compromise the validity and reproducibility of research findings.
• Current terminology for zebrafish genetic backgrounds lacks standardization compared to other model organisms.

Conclusions:

• Adequate control and detailed reporting of zebrafish genetic backgrounds are essential for improving research transparency and reproducibility.
• Adoption of genetic monitoring is recommended for characterizing existing lines and detecting contamination.
• Standardized nomenclature and genetic characterization will enhance the utility of zebrafish (Danio rerio) in scientific research.