Detection and mapping of quantitative trait loci that determine responsiveness of mice to nitrous oxide antinociception

• Published in: Neuroscience Vol. 123; no. 3; pp. 743 - 749
• Main Authors: Mueller, J.L, Ellenberger, E.A, Vaughn, L.K, Belknap, J.K, Quock, R.M
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2004; Elsevier
• Subjects: Animals; antinociception; Biological and medical sciences; Chromosome Mapping - methods; Female; Fundamental and applied biological sciences. Psychology; Genotype; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; nitrous oxide; Nitrous Oxide - pharmacology; Pain Measurement - drug effects; Pain Measurement - methods; quantitative trait loci; Quantitative Trait Loci - drug effects; Quantitative Trait Loci - genetics; Vertebrates: nervous system and sense organs; LOD; dom; NOS; antinociception; B6; nitrous oxide; var; QTL; cM; quantitative trait loci; mice; D2; Vertebrata; Mammalia; Mouse; Animal; Rodentia
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2003.10.020

Exposure to 70% N
2O evokes a robust antinociceptive effect in C57BL/6 (B6) but not in DBA/2 (D2) inbred mice. This study was conducted to identify quantitative trait loci (QTL) in the mouse genome that might determine responsiveness to N
2O. Offspring from the F
2 generation bred from B6 and D2 progenitors exhibited a broad range of responsiveness to N
2O antinociception as determined by the acetic acid-induced abdominal constriction test. QTL analysis was then used to dissect this continuous trait distribution into component loci, and to map them to broad chromosomal regions. To this end, 24 spleens were collected from each of the following four groups: male and female F
2 mice responding to 70% N
2O in oxygen with 100% response (high-responders); and male and female F
2 mice responding with 0% response (low-responders). Genomic DNA was extracted from the spleens and genotyped with simple sequence length polymorphism MapPairs markers. Findings were combined with findings from the earlier QTL analysis from BXD recombinant inbred mice [Brain Res 725 (1996) 23]. Combined results revealed two significant QTL that influence responsiveness to nitrous oxide on proximal chromosome 2 and distal chromosome 5, and one suggestive QTL on midchromosome 18. The chromosome 2 QTL was evident only in males. A significant interaction was found between a locus on chromosome 6 and another on chromosome 13 with a substantial effect on N
2O antinociception.