Genetic background influences phenotypes
As seen below, mutations introgressed on different backgrounds result in different phenotypes: a diabetes mutation on a C57BL/6J background results in obesity with transient diabetes, but on a C57BLKS/J background, the same mutation results in obesity with overt diabetes; an obesity mutation on a C57BL/6J background results in obesity with transient diabetes, but on a C57BLKS/J background, the same mutation results in obesity with overt diabetes.
Genetic backgrounds affects results
As the number of mouse strains and substrains increases, attention to genetic background will be increasingly more important. Otherwise, research results will either be confounding or unreliable (Gerlai 2001; Linder 2001; Wolfer et al. 2002). Although a fair amount of confounding research is probably never reported, examples of reported studies include the following:
- Wasted research effort because of a mix-up in the AL/N substrains (Bailey 1982. Immunol Today 3:210-14)
- Confounded results because of variablility in 129 substrains (Hogan et al. 1994. Manipulating the mouse embryo: a laboratory manual, 2nd ed. Cold Spring Harbor (NY); Threadgill et al. 1997)
- Dubious results because of C57BL substrain differences (Specht and Schoepfer 2001; Wotjak 2003)
Carefully choose appropriate genetic backgrounds and controls
Many resources can help you choose the most appropriate genetic backgrounds and controls for your experiments, including the following:
Remember that linked genes can differ between experimental models and controls, and that, in some cases, it may be a good idea to test alleles on several backgrounds. Try to follow the recommendations of the Banbury Conference (Silva et al. 1997):
Include a detailed description of the genetic background of the mice you study in all your publications and communications.
Use a common background so that your experiments can be replicated.
This manual explains the importance of using genetically well-defined mice for biomedical research, describes The Jackson Laboratory's resources for helping researchers choose those mice, encourages researchers to clearly communicate the genetic make-up of their models by using proper nomenclature, and summarizes The Jackson Laboratory's programs to ensure that JAX® Mice are genetically well-defined.