TY - JOUR
T1 - Nitrous oxide antinociception in BXD recombinant inbred mouse strains and identification of quantitative trait loci
AU - Quock, Raymond M.
AU - Mueller, Janet L.
AU - Vaughn, Linda K.
AU - Belknap, John K.
N1 - Funding Information:
This research was supported by NIH Grants DE-06894 (RMQ) and BRSG SO7RR 05369 (RMQ) and a Merit Review grant from the Department of Veterans Affairs (JKB). We also thank Dr. Richard M. Weinshilboum (Mayo Clinic/Mayo Medical School, Rochester, MN) and Dr. Jeanne M. Wehner (University of Colorado, Boulder, CO) for their suggestions and helpful comments, Dr. Edwin H. Chen (University of Illinois at Chicago School of Public Health) for help with the cluster analysis, and Dr. Steve Mitchell (Oregon Health Sciences University and V.A. Medical Center, Portland, OR) for carrying out the QTL analysis.
PY - 1996/6/24
Y1 - 1996/6/24
N2 - Among inbred mouse strains, DBA/2 mice are unique because of their poor responsiveness to nitrous oxide (N2O) antinociception. As a first step towards identifying candidate genes involved in determining antinociceptive responsiveness to N2O, male mice from the DBA/2 strain, the more responsive C57BL/6 strain, their B6D2F~1 offspring, and 22 BXD recombinant inbred (RI) strains derived from DBA/2 and C57BL/6 mice were exposed to N2O and evaluated using the acetic acid abdominal constriction test. When exposed to 70% N2O, C57BL/6, DBA/2 and B6D2F1 mice exhibited antinociceptive responses of 78. 22 and 55%, respectively. The BXD RI strains demonstrated varying degrees of responsiveness to N2O. Cluster analysis revealed one cluster of 16 strains approximating the C57BL/6 progenitor (61.9-100% antinociceptive response to 70% N2O) and another of six strains around the DBA/2 progenitor (9.1-40% antinociceptive 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 existing mouse RI strains, we found associations at the 0.01 level on seven chromosomes with the most promising marker loci being Il2ra, Hbb, Hmglrs7 and Gsl5 on chromosomes 2, 7, 16 and 19, respectively (P < 0.002).
AB - Among inbred mouse strains, DBA/2 mice are unique because of their poor responsiveness to nitrous oxide (N2O) antinociception. As a first step towards identifying candidate genes involved in determining antinociceptive responsiveness to N2O, male mice from the DBA/2 strain, the more responsive C57BL/6 strain, their B6D2F~1 offspring, and 22 BXD recombinant inbred (RI) strains derived from DBA/2 and C57BL/6 mice were exposed to N2O and evaluated using the acetic acid abdominal constriction test. When exposed to 70% N2O, C57BL/6, DBA/2 and B6D2F1 mice exhibited antinociceptive responses of 78. 22 and 55%, respectively. The BXD RI strains demonstrated varying degrees of responsiveness to N2O. Cluster analysis revealed one cluster of 16 strains approximating the C57BL/6 progenitor (61.9-100% antinociceptive response to 70% N2O) and another of six strains around the DBA/2 progenitor (9.1-40% antinociceptive 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 existing mouse RI strains, we found associations at the 0.01 level on seven chromosomes with the most promising marker loci being Il2ra, Hbb, Hmglrs7 and Gsl5 on chromosomes 2, 7, 16 and 19, respectively (P < 0.002).
KW - Antinoception
KW - Inbred mouse strains
KW - Nitrous oxide
KW - Quantitative trait loci
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U2 - 10.1016/0006-8993(96)00211-9
DO - 10.1016/0006-8993(96)00211-9
M3 - Article
C2 - 8828582
AN - SCOPUS:0030600009
SN - 0006-8993
VL - 725
SP - 23
EP - 29
JO - Brain Research
JF - Brain Research
IS - 1
ER -