Abolished InsP3R2 function inhibits sweat secretion in both humans and mice

Klar, Joakim (author): Uppsala universitet,Medicinsk genetik,Science for Life Laboratory, SciLifeLab

Hisatsune, Chihiro (author)

Baig, Shahid M. (author)

Tariq, Muhammad (author)

Johansson, Anna C. V. (author): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi

Rasool, Mahmood (author)

Malik, Naveed Altaf (author)

Ameur, Adam (author): Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab

Sugiura, Kotomi (author)

Feuk, Lars (author): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Genomik

Mikoshiba, Katsuhiko (author)

Dahl, Niklas (author): Uppsala universitet,Medicinsk genetik,Science for Life Laboratory, SciLifeLab

(creator_code:org_t)

2014
2014
English.
In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 124:11, s. 4773-4780

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Klar, Joakim; Hisatsune, Chihi ...; Baig, Shahid M.; Tariq, Muhammad; Johansson, Anna ...; Rasool, Mahmood; show more...; Malik, Naveed Al ...; Ameur, Adam; Sugiura, Kotomi; Feuk, Lars; Mikoshiba, Katsu ...; Dahl, Niklas; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Other Clinical M ...

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