{"entity": "publication", "iuid": "ee38afb802cf41a3b90de64ccbb53f24", "timestamp": "2026-09-12T20:31:44.850Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee38afb802cf41a3b90de64ccbb53f24.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee38afb802cf41a3b90de64ccbb53f24"}}, "title": "Abolished InsP3R2 function inhibits sweat secretion in both humans and mice.", "authors": [{"family": "Klar", "given": "Joakim", "initials": "J"}, {"family": "Hisatsune", "given": "Chihiro", "initials": "C"}, {"family": "Baig", "given": "Shahid M", "initials": "SM"}, {"family": "Tariq", "given": "Muhammad", "initials": "M"}, {"family": "Johansson", "given": "Anna C V", "initials": "AC"}, {"family": "Rasool", "given": "Mahmood", "initials": "M"}, {"family": "Malik", "given": "Naveed Altaf", "initials": "NA"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Sugiura", "given": "Kotomi", "initials": "K"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Mikoshiba", "given": "Katsuhiko", "initials": "K"}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2014-11-00", "journal": {"volume": "124", "issn": "1558-8238", "issue": "11", "pages": "4773-4780", "title": "J. Clin. Invest.", "issn-l": "0021-9738"}, "abstract": "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.", "doi": "10.1172/JCI70720", "pmid": "25329695", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "70720"}, {"db": "pmc", "key": "PMC4347256"}], "notes": [], "created": "2017-05-04T15:02:42.254Z", "modified": "2021-07-07T14:37:06.641Z"}