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Genetic background variability is a major—and often overlooked—source of irreproducibility in studies using genetically modified mice. This paper explains how genetic drift, substrain differences, human error, and insufficient background documentation can lead to unexpected phenotypes, misinterpretation of results, and non-reproducible data, even among commonly used strains like C57BL/6. Drawing on extensive published research, it outlines why routine genetic monitoring is essential and describes best practices for maintaining strain integrity, including SNP-based monitoring, allele-specific genotyping, and disciplined colony management. Together, these approaches help researchers protect data quality, reduce risk, and ensure confidence in experimental outcomes.
