Positional cloning of a quantitative trait locus contributing to pain sensitivity: possible mediation by Tyrp1

Genes, Brain, and Behavior
A FortinJ S Mogil

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

Jan 1, 1992·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·H Z Hill
Aug 1, 1966·The Journal of Investigative Dermatology·A S BreathnachL M Wyllie
Oct 1, 1996·The Journal of Experimental Medicine·M HaraB A Gilchrest
Mar 4, 2000·Nature Genetics·J H NadeauE S Lander
Mar 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey S MogilRoger B Fillingim
Apr 11, 2003·Clinics in Chest Medicine·Franklin A Michota
Mar 18, 2005·The Journal of Pain : Official Journal of the American Pain Society·Roger B FillingimMargaret R Wallace
Aug 16, 2005·Pain·Jeffrey S Mogil, Mona Lisa Chanda
Aug 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey S MogilPeter W Reeh
Jun 3, 2006·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Luda DiatchenkoWilliam Maixner
Oct 24, 2006·Nature Medicine·Irmgard TegederClifford J Woolf
Nov 21, 2007·Trends in Genetics : TIG·Luda DiatchenkoWilliam Maixner
Dec 19, 2007·Biochemical and Biophysical Research Communications·Koji MakinoHiroyuki Nakanishi
Jul 1, 2008·Nature Reviews. Drug Discovery·Mitchell B Max, Walter F Stewart
Oct 7, 2008·Annual Review of Pharmacology and Toxicology·Michael L Lacroix-Fralish, Jeffrey S Mogil

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Citations

Apr 25, 1992·Lancet·G W Hanks, D M Justins
Apr 5, 2012·European Journal of Pain : EJP·C A DominguezF Piehl
Dec 30, 2011·PLoS Neglected Tropical Diseases·Ruben Ramirez-AquinoIrma Aguilar-Delfin
Feb 10, 2018·Frontiers in Molecular Neuroscience·Kai K KummerMichiel Langeslag

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