NITROUS-OXIDE ANTINOCICEPTION IN BXD RECOMBINANT INBRED MOUSE STRAINSAND IDENTIFICATION OF QUANTITATIVE TRAIT LOCI

Among inbred mouse strains, DBA/2 mice are unique because of their poo r responsiveness to nitrous oxide (N2O) antinociception. As a first st ep towards identifying candidate genes involved in determining antinoc iceptive responsiveness to N2O, male mice from the DBA/2 strain, the m ore responsive C57BL/6 strain, their B6D2F(1) offspring, and 22 BXD re combinant inbred (RI) strains derived from DBA/2 and C57BL/6 mice were exposed to N2O and evaluated using the acetic acid abdominal constric tion test. When exposed to 70% N2O, C57BL/6, DBA/2 and B6D2F(1) mice e xhibited antinociceptive responses of 78, 22 and 55%, respectively. Th e BXD RI strains demonstrated varying degrees of responsiveness to N2O . Cluster analysis revealed one cluster of 16 strains approximating th e C57BL/6 progenitor (61.9-100% antinociceptive response to 70% N2O) a nd another of six strains around the DBA/2 progenitor (9.1-40% antinoc iceptive response to 70% N2O). The robust strain differences permitted screening the strain means with 1492 marker loci previously mapped in BXD RI strains. Using a QTL analysis specifically tailored to existin g mouse RI strains, we found associations at the 0.01 level on seven c hromosomes with the most promising marker loci being Il2ra, Hbb, Hmg1r s7 and Gsl5 on chromosomes 2, 7, 16 and 19, respectively (P < 0.002).