Positional cloning of a quantitative trait locus contributing to pain sensitivity: possible mediation by Tyrp1
Abstract
To identify novel pain-relevant genes, a set of 35 recombinant congenic strains derived from the sensitive C57BL/6 and resistant A/J strains were tested for their sensitivity to noxious heat on the radiant heat paw-withdrawal test. Nine strains were found to display differential sensitivity, and the two most extreme responders were used to generate independent secondary crosses for quantitative trait locus (QTL) mapping. From these genetic analyses, a QTL, which we call Tpnr5, was mapped to a 14-Mb interval of mouse chromosome 4 containing 39 genes. In addition to the paw-withdrawal test phenotype, Tpnr5 may be relevant to mechanical and inflammatory nociception. A series of strategies - including in silico analyses, reverse transcriptase polymerase chain reaction (RT-PCR) in multiple tissues and exonic DNA sequencing - were used to generate a list of six prioritized candidate genes. One of these, tyrosinase-related protein 1 (Tyrp1), displayed enriched expression in the dorsal root ganglia, an inactivating (C110Y) mutation in the resistant A/J strain, and a null mutant found to be more resistant to thermal nociception compared to its wild-type counterpart. Although other genes cannot be definitively ruled out, existing data ar...Continue Reading
References
The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans
Citations
Related Concepts
Related Feeds
Amygdala and Midbrain Dopamine
The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.
Amygdala: Sensory Processes
Amygdalae, nuclei clusters located in the temporal lobe of the brain, play a role in memory, emotional responses, and decision-making. Here is the latest research on sensory processes in the amygdala.