Exploring gene-environment interaction in stress-response behaviour in canine and fish models

Understanding the biological underpinnings of gene-environment interactions (GxE) in humans is challenging. Therefore, animal models, with their controlled genetic backgrounds and environments can provide invaluable insights. This study aims to identify the genetic background of a particular “freezing” behaviour observed in beagle dogs, as a mechanism coping with stress. An intriguing observation was made in 50 kennel-raised beagles: upon leaving the kennel, 14 exhibited "freezing" behaviour and remained immobile during the 30-minute test, while 9 showed normal activity and 27 dogs were initially immobile but later relaxed and began to move. Given the uniform housing conditions and care, the differences observed are most likely attributable to genetic factors. A genome-wide association study (GWAS) identified an intronic SNP on the KCNQ3 gene linked to the "freezing" behaviour. Examination of genomic DNA and cDNA from the brain tissues of "freezing" dogs did not reveal mutations in the coding sequence (CDS) of the KCNQ3 gene. Notably, dogs from the same genetic pool raised in family settings did not exhibit the “freezing” behaviour, suggesting that the adverse effects of the causative mutations can be mitigated by more favourable environmental conditions. To test whether KCNQ3 could be linked to the phenotype despite the absence of CDS-altering mutations, we extended our study to zebrafish. We demonstrate that kcnq3-deficient fish exhibit fear reactions in novel environments, indicating a significant role for Kcnq3 in regulating fear responses across vertebrate species. Similar GxE studies could lead to personalized treatments tailored to individual genetic and environmental profiles.