title: Sensory Neuron-Specific Deletion of TRPA1 Results in Mechanical Cutaneous Sensory Deficits.
abstract: The nonselective cation channel transient receptor potential ankyrin 1 (TRPA1) is known to be a key contributor to both somatosensation and pain. Recent studies have implicated TRPA1 in additional physiologic functions and have also suggested that TRPA1 is expressed in nonneuronal tissues. Thus, it has become necessary to resolve the importance of TRPA1 expressed in primary sensory neurons, particularly since previous research has largely used global knock-out animals and chemical TRPA1 antagonists. We therefore sought to isolate the physiological relevance of TRPA1 specifically within sensory neurons. To accomplish this, we usedAdvillin-Cremice, in which the promoter for Advillin is used to drive expression of Cre recombinase specifically within sensory neurons. TheseAdvillin-Cremice were crossed withTrpa1fl/flmice to generate sensory neuron-specificTrpa1knock-out mice. Here, we show that tissue-specific deletion of TRPA1 from sensory neurons produced strong deficits in behavioral sensitivity to mechanical stimulation, while sensitivity to cold and heat stimuli remained intact. The mechanical sensory deficit was incomplete compared to the mechanosensory impairment of TRPA1 global knock-out mice, in line with the incomplete (∼80%) elimination of TRPA1 from sensory neurons in the tissue-specificAdvillin-Creknock-out mice. Equivalent findings were observed in tissue-specific knock-out animals originating from two independently-generatedAdvillin-Crelines. As such, our results show that sensory neuron TRPA1 is required for mechanical, but not cold, responsiveness in noninjured skin.
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin , Milwaukee, WI 53226.
authors.forename: Katherine J
authors.identifier: 0000-0002-4419-4834
authors.initials: KJ
authors.lastname: Zappia
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin , Milwaukee, WI 53226.
authors.forename: Crystal L
authors.identifier: 0000-0002-0868-2582
authors.initials: CL
authors.lastname: O'Hara
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin , Milwaukee, WI 53226.
authors.forename: Francie
authors.identifier: 0000-0002-0071-5685
authors.initials: F
authors.lastname: Moehring
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey , Piscataway, NJ 08854.
authors.forename: Kelvin Y
authors.identifier: 0000-0002-8617-5543
authors.initials: KY
authors.lastname: Kwan
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin , Milwaukee, WI 53226.
authors.forename: Cheryl L
authors.identifier: 0000-0003-4966-6594
authors.initials: CL
authors.lastname: Stucky
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003080:Cold Temperature; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D008159:Lumbar Vertebrae; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology*; D012867:Skin / Q000294:innervation* / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D014110:Touch / Q000187:drug effects / Q000502:physiology*; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000172:deficiency* / Q000235:genetics
chemical_list: C113762:Avil protein, mouse; D008840:Microfilament Proteins; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D002118:Calcium
keywords: TRPA1; advillin; cold; mechanical; sensory neuron; somatosensation