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Abolished InsP3R2 f...
Abolished InsP3R2 function inhibits sweat secretion in both humans and mice
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- Klar, Joakim (author)
- Uppsala universitet,Medicinsk genetik,Science for Life Laboratory, SciLifeLab
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Hisatsune, Chihiro (author)
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Baig, Shahid M. (author)
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Tariq, Muhammad (author)
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- Johansson, Anna C. V. (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
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Rasool, Mahmood (author)
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Malik, Naveed Altaf (author)
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- Ameur, Adam (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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Sugiura, Kotomi (author)
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- Feuk, Lars (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Genomik
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Mikoshiba, Katsuhiko (author)
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- Dahl, Niklas (author)
- Uppsala universitet,Medicinsk genetik,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2014
- 2014
- English.
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In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 124:11, s. 4773-4780
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- There are 3 major sweat-producing glands present in skin; eccrine, apocrine, and apoeccrine glands. Due to the high rate of secretion, eccrine sweating is a vital regulator of body temperature in response to thermal stress in humans; therefore, an inability to sweat (anhidrosis) results in heat intolerance that may cause impaired consciousness and death. Here, we have reported 5 members of a consanguineous family with generalized, isolated anhidrosis, but morphologically normal eccrine sweat glands. Whole-genome analysis identified the presence of a homozygous missense mutation in ITPR2, which encodes the type 2 inositol 1,4,5-trisphosphate receptor (InsP3R2), that was present in all affected family members. We determined that the mutation is localized within the pore forming region of InsP3R2 and abrogates Ca2+ release from the endoplasmic reticulum, which suggests that intracellular Ca2+ release by InsP3R2 in clear cells of the sweat glands is important for eccrine sweat production. Itpr2–/– mice exhibited a marked reduction in sweat secretion, and evaluation of sweat glands from Itpr2–/– animals revealed a decrease in Ca2+ response compared with controls. Together, our data indicate that loss of InsP3R2-mediated Ca2+ release causes isolated anhidrosis in humans and suggest that specific InsP3R inhibitors have the potential to reduce sweat production in hyperhidrosis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Other Clinical Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Klar, Joakim
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Hisatsune, Chihi ...
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Baig, Shahid M.
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Tariq, Muhammad
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Johansson, Anna ...
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Rasool, Mahmood
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show more...
-
Malik, Naveed Al ...
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Ameur, Adam
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Sugiura, Kotomi
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Feuk, Lars
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Mikoshiba, Katsu ...
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Dahl, Niklas
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Other Clinical M ...
- Articles in the publication
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Journal of Clini ...
- By the university
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Uppsala University