DOR-EGFP reporter mice have an enhanced green fluorescent protein (EGFP) knocked into the last exon of the opioid receptor, delta 1 (Oprd1) gene. DOR-EGFP mice have EGFP inserted just upstream of the stop codon of the targeted gene, allowing this strain to express endogenous Oprd1-encoded receptors with a fused EGFP at the C-terminus. Mice homozygous for this allele are viable and fertile. δ-opioid receptors (DORs) are G-protein-coupled receptors that inhibit neuronal activity upon binding of ligands such as enkephalins and other opioids. DORs are targets for the treatment of chronic pain, drug abuse, and emotional disorders.
Mice emit EGFP fluorescence in neurons in the caudate putamen at birth, in the hippocampus at day 3 after birth, with increasing expression throughout the brain reaching maximal intensity at day 15. Although, Oprd1 transcription, receptor numbers, and activation is slightly increased in DOR-EGFP mice compared to wild-type animals, affinity of the receptor for agonists and endogenous peptides is unchanged. Treatment with receptor agonists triggers receptor internalization, with cell surface fluorescence decreasing in a dose-dependent manner. This correlates with a rapid and dose-dependent increase of locomotor activity. Mice with internalized receptors are insensitive to subsequent agonist administration.
When crossed to MOR-mCherry mice (Stock No. 029013), expressing mCherry in mu opioid receptors, bicolor double mutant mice (DOR-eGFP/MORmcherry) express functional fluorescent forms of the two receptors.
