Faculty Collaboration Database

Mechanosensory and ATP Release Deficits following Keratin14-Cre-Mediated TRPA1 Deletion Despite Absence of TRPA1 in Murine Keratinocytes. PLoS One 2016;11(3):e0151602

Date

03/16/2016

Pubmed ID

26978657

Pubmed Central ID

PMC4792390

DOI

10.1371/journal.pone.0151602

Scopus ID

2-s2.0-84961820405 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

Keratinocytes are the first cells that come into direct contact with external tactile stimuli; however, their role in touch transduction in vivo is not clear. The ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) is essential for some mechanically-gated currents in sensory neurons, amplifies mechanical responses after inflammation, and has been reported to be expressed in human and mouse skin. Other reports have not detected Trpa1 mRNA transcripts in human or mouse epidermis. Therefore, we set out to determine whether selective deletion of Trpa1 from keratinocytes would impact mechanosensation. We generated K14Cre-Trpa1fl/fl mice lacking TRPA1 in K14-expressing cells, including keratinocytes. Surprisingly, Trpa1 transcripts were very poorly detected in epidermis of these mice or in controls, and detection was minimal enough to preclude observation of Trpa1 mRNA knockdown in the K14Cre-Trpa1fl/fl mice. Unexpectedly, these K14Cre-Trpa1fl/fl mice nonetheless exhibited a pronounced deficit in mechanosensitivity at the behavioral and primary afferent levels, and decreased mechanically-evoked ATP release from skin. Overall, while these data suggest that the intended targeted deletion of Trpa1 from keratin 14-expressing cells of the epidermis induces functional deficits in mechanotransduction and ATP release, these deficits are in fact likely due to factors other than reduction of Trpa1 expression in adult mouse keratinocytes because they express very little, if any, Trpa1.

Author List

Zappia KJ, Garrison SR, Palygin O, Weyer AD, Barabas ME, Lawlor MW, Staruschenko A, Stucky CL

Authors

Michael W. Lawlor MD, PhD Adjunct Professor in the Pathology department at Medical College of Wisconsin
Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Afferent Pathways
Animals
Animals, Congenic
Arthritis, Experimental
Epidermis
Freund's Adjuvant
Gene Expression Profiling
Gene Knockdown Techniques
Genes, Reporter
Integrases
Keratinocytes
Mechanoreceptors
Mechanotransduction, Cellular
Mice
Mice, Inbred C57BL
Nociception
Organ Specificity
Pain Threshold
Physical Stimulation
RNA, Messenger
Sensory Receptor Cells
Skin
TRPA1 Cation Channel
Transient Receptor Potential Channels