The Dcc gene is large and extends over 1.09 MB of chromosome 18. The highly correlated haplotype block is near the 5’ end of the first intron. The Dcc gene encodes a receptor for the axonal guidance cue netrin-1, which is best described for its role in the organization of neuronal connectivity during development, but it has also been shown to play a role in behavioral and synaptic plasticity in the adult brain [21, 25–27]. DCC-mediated netrin-1 signaling is also implicated in cell migration, cell death, and angiogenesis [19, 26–29]. Two SNPs in this gene induce amino acid changes. Further analysis revealed that the variation pattern of these two amino acid changing SNPs divided the 23 strains into 3 groups with low (<0.5), low and high (>0.5) fractional changes in baseline mechanical nociceptive thresholds after administration of morphine (Additional file 2: Figure S2). All three strains with the A713V amino acid substitution were highly resistant to OIH measured using both thermal and mechanical stimuli, and showed little development of tolerance as well.
