Genotype-Specific Electroretinogram Signatures in Drosophila: Implications for Neurodegeneration Models Using w1118 Backgrounds

Drosophila melanogaster serves as a powerful model for studying neurodegenerative diseases, often employing the GAL4-UAS system for targeted gene expression. Electroretinograms (ERGs) provide a robust in vivo functional readout of neuronal integrity and are increasingly used to assess disease progression and therapeutic interventions in these models. However, the genetic background upon which these models are built, particularly the widely used w1118 white-eyed mutant, can significantly influence baseline ERG characteristics. This study systematically characterizes ERG responses in wild-type Canton S (CS), w1118, and a w1118line carrying a UAS-hPLD1 construct (which includes a mini-white gene). We demonstrate profound differences in ERG amplitudes, waveforms, and responses to varying light stimuli (intensity and duration) between these genotypes, as well as significant sex-specific variations. Notably, w1118 flies exhibit markedly larger ERG amplitudes compared to CS, while the hPLD1 line shows partial compensation. We also introduce a novel quadrant-based analysis of the receptor potential, revealing distinct "fingerprints" for each genotype. These findings underscore that the w1118 background is not electrophysiologically neutral and can intrinsically alter neuronal responses. This has critical implications for interpreting ERG data from neurodegeneration models, as these background effects could mask or mimic disease-related changes. Researchers must consider these baseline differences and potential sex-specific effects to accurately attribute observed ERG phenotypes to the gene or condition under investigation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/626125v2_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1b655f0org.highwire.dtl.DTLVardef@1c412e7org.highwire.dtl.DTLVardef@1b52fe3org.highwire.dtl.DTLVardef@5af680_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIERG profiles differ significantly between CS, w1118, and w1118; UAS-hPLD1 flies. C_LIO_LIThe w1118 background, common in GAL4-UAS studies, exhibits distinct ERG features. C_LIO_LISex-specific differences in ERG responses are prominent and genotype-dependent. C_LIO_LIUAS-hPLD1 insertion (with mini-white) partially alters the w1118 ERG phenotype. C_LIO_LIResults caution the interpretation of ERG data in w1118 neurodegeneration models. C_LI