Inbred mice are preferred over outbred mice because it is assumed that they display less trait variability. We compared coefficients of variation and did not find evidence of greater trait stability in inbred mice. We conclude that contrary to conventional wisdom, outbred mice might be better subjects for most biomedical research.

The laboratory mouse is the most commonly used nonhuman experimental subject in biomedical research 1. For many decades, inbred mouse strains have been preferred over outbred stocks, with particular strains such as C57BL/6 and BALB/c used in wide-ranging biomedical applications 2. Inbred mice are preferentially chosen for immunological studies (to prevent alloimmune responses), population genetic mapping (to allow diallele crosses for known genetic markers), and molecular genetic studies (to avoid background effects in mutagenesis and transgenics). The more general preference for inbred strains across biomedicine stems from the conventional wisdom that these animals should demonstrate less within-strain phenotypic variability than outbred animals, because in any given inbred strain phenotypic variability (V p) equals environmental variability (V e), whereas in outbred animals genetic variability (V g) is present in addition to V e and gene–environment interaction (V ge). If this assumption were valid, statistical power could be maintained with fewer inbred mice compared with the number needed in outbred-strain-based experiments, which would present practical and ethical advantages. However, the evidence for lower phenotypic variability among inbred mice is mixed, with some early (eg, ref. 3) and more recent (eg, ref. 4) studies explicitly suggesting otherwise. Nonetheless, the idea that genetic heterogeneity leads to greater phenotypic variability is compelling, and its proponents argue against the use of outbred stocks in biomedical research (eg, refs 5, 6, 7).