The importance of genetic background

Genetic background influences phenotypes

Mutations introgressed on different backgrounds result in different phenotypes. For example, a diabetes mutation (Lepr^db) 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. Likewise, an obesity mutation (Lep^ob) on the C57BL/6J background results in obesity with transient diabetes, but results in obesity with overt diabetes when transferred to the C57BLKS/J background.

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 AL/N substrains (Bailey 1982. Immunol Today 3:210-14)
• Confounded results because of variability in 129 substrains (Hoganet al. 1994. Manipulating the mouse embryo: a laboratory manual, 2nd ed. Cold Spring Harbor (NY); Threadgill et al. 1997)
• Dubious results due to C57BL/6 substrain differences (Specht and Schoepfer 2001; Wotjak 2003)

Carefully choose appropriate genetic backgrounds and controls

• The Mouse Phenome Database

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.
• Choose a common genetic background so that your experiments can be easily replicated across trials and among different laboratories.