Unpredictable effects of the genetic background of transgenic lines in physiological quantitative traits
Most physiology, fitness and disease phenotypes are considered complex traits since they exhibit continuous variation in natural populations. The use of homozygous inbred strains allows the assessment of the impact of genetic composition on complex phenotypes. Nevertheless, to understand gene function, we often combine transgenic lines to assess the phenotype of interest in a heterozygous state. Here, using inbred wild-type Drosophila strains, we assessed the phenotypic variation of six physiology and fitness traits: female fecundity, survival and intestinal mitosis upon oral infection, defecation rate and fecal pH upon oral infection, and terminal tracheal cell branching in hypoxia. Indeed, we found continuous variation in all traits tested. To estimate the extent to which small genetic background differences affected these traits, we assessed the effects of commonly used Drosophila UAS-RNAi transgenic strains and their backcrossed isogenized counterparts in the same assays. We tested 20 non-isogenic strains (10 KK and 10 GD) from the Vienna Drosophila Resource Center and their isogenic counterparts without Gal4 induction and found that the different phenotypes were variably sensitive to the genetic background. For example, survival upon infection and female fecundity exhibited differences in 50% and 40% of the tested isogenic vs. non-isogenic pairs, respectively, whereas all other phenotypes were affected in only 10-25% of the cases. We also observed that the genetic background affects Gal4 transgenes unpredictably. Thus, depending on the trait of interest, the genetic background of commonly used transgenic strains needs to be considered carefully during experimentation.