Genetic variability of canine NR3C1 gene and its role in glucocorticoid signaling
Keywords:
dogs, NR3C1 gene, stress response, corticosteroids, polymorphismsAbstract
The glucocorticoid receptor is a ligand-activated transcription factor that mediates the actions of glucocorticoids and regulates genes involved in metabolism, development, inflammation, and the immune response. Glucocorticoids are lipophilic, allowing them to freely cross cell membranes and bind to glucocorticoid receptors, which, upon translocation to the nucleus, enhance or suppress transcription of target genes. The glucocorticoid receptor is encoded by the NR3C1 gene, which has been identified in both humans and dogs. This gene is located on canine chromosome 2 and contains nine exons. The NR3C1 gene encodes multiple glucocorticoid receptor isoforms via alternative splicing and alternative translation initiation, leading to diverse cellular and physiological responses. Previous studies of NR3C1 gene polymorphisms have been conducted in the context of various human diseases, such as rheumatoid arthritis, multiple sclerosis, and an increased risk of major depression. In dogs, identified polymorphisms have been investigated in relation to immune thrombocytopenia and in clinical studies evaluating dogs’ responses to steroid medications. Since glucocorticoids such as cortisol are key mediators of the hypothalamic-pituitary-adrenal (HPA) axis and play a central role in the physiological adaptation to stress, variations in the NR3C1 gene may influence receptor sensitivity, feedback regulation, and overall stress reactivity in dogs. Investigating the occurrence of genetic variants and the relationship between NR3C1 polymorphisms, cortisol levels, and behavioural indicators of stress may provide valuable insights into canine stress physiology and support the development of more individualized approaches to animal welfare assessment and veterinary treatment. Particular attention should be given to indigenous dog breeds, which represent unique genetic resources shaped by long-term adaptation to specific environmental conditions and management practices, and may therefore harbour distinct genetic variants associated with stress resilience and adaptive capacity.
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