Reduced spontaneous itch in mouse models of cholestasis

Abstract Pruritus is one of the most distressing symptoms in cholestatic patients. Plasma autotaxin (ATX) activity correlates with the severity of pruritus in cholestatic patients, but the pathophysiology is unclear. To study pruritus in mice, we measured scratch activity in cholestatic Atp8b1 mutan...

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Autores principales: Jacqueline Langedijk, Ruth Bolier, Dagmar Tolenaars, Lysbeth ten Bloemendaal, Suzanne Duijst, Dirk de Waart, Ulrich Beuers, Piter Bosma, Ronald Oude Elferink
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/8a91086451c548c488f3ed16188f6c17
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spelling oai:doaj.org-article:8a91086451c548c488f3ed16188f6c172021-12-02T17:05:00ZReduced spontaneous itch in mouse models of cholestasis10.1038/s41598-021-85660-12045-2322https://doaj.org/article/8a91086451c548c488f3ed16188f6c172021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85660-1https://doaj.org/toc/2045-2322Abstract Pruritus is one of the most distressing symptoms in cholestatic patients. Plasma autotaxin (ATX) activity correlates with the severity of pruritus in cholestatic patients, but the pathophysiology is unclear. To study pruritus in mice, we measured scratch activity in cholestatic Atp8b1 mutant mice, a model for Progressive Familial Intrahepatic Cholestasis type 1, and wild type mice (WT) with alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. To induce cholestasis, Atp8b1 mutant mice received a diet containing 0.1% cholic acid (CA) and WT mice were treated with ANIT. In these mice ATX was also overexpressed by transduction with AAV-ATX. Scratch activity was measured using an unbiased, electronic assay. Marked cholestasis was accomplished in both Atp8b1 mutant mice on a CA-supplemented diet and in ANIT-treatment in WT mice, but scratch activity was decreased rather than increased while plasma ATX activity was increased. Plasma ATX activity was further increased up to fivefold with AAV-ATX, but this did not induce scratch activity. In contrast to several reports two cholestatic mouse models did not display increased scratch activity as a measure of itch perception. Increasing plasma ATX activity by overexpression also did not lead to increased scratch activity in mice. This questions whether mice are suitable to study cholestatic itch.Jacqueline LangedijkRuth BolierDagmar TolenaarsLysbeth ten BloemendaalSuzanne DuijstDirk de WaartUlrich BeuersPiter BosmaRonald Oude ElferinkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jacqueline Langedijk
Ruth Bolier
Dagmar Tolenaars
Lysbeth ten Bloemendaal
Suzanne Duijst
Dirk de Waart
Ulrich Beuers
Piter Bosma
Ronald Oude Elferink
Reduced spontaneous itch in mouse models of cholestasis
description Abstract Pruritus is one of the most distressing symptoms in cholestatic patients. Plasma autotaxin (ATX) activity correlates with the severity of pruritus in cholestatic patients, but the pathophysiology is unclear. To study pruritus in mice, we measured scratch activity in cholestatic Atp8b1 mutant mice, a model for Progressive Familial Intrahepatic Cholestasis type 1, and wild type mice (WT) with alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. To induce cholestasis, Atp8b1 mutant mice received a diet containing 0.1% cholic acid (CA) and WT mice were treated with ANIT. In these mice ATX was also overexpressed by transduction with AAV-ATX. Scratch activity was measured using an unbiased, electronic assay. Marked cholestasis was accomplished in both Atp8b1 mutant mice on a CA-supplemented diet and in ANIT-treatment in WT mice, but scratch activity was decreased rather than increased while plasma ATX activity was increased. Plasma ATX activity was further increased up to fivefold with AAV-ATX, but this did not induce scratch activity. In contrast to several reports two cholestatic mouse models did not display increased scratch activity as a measure of itch perception. Increasing plasma ATX activity by overexpression also did not lead to increased scratch activity in mice. This questions whether mice are suitable to study cholestatic itch.
format article
author Jacqueline Langedijk
Ruth Bolier
Dagmar Tolenaars
Lysbeth ten Bloemendaal
Suzanne Duijst
Dirk de Waart
Ulrich Beuers
Piter Bosma
Ronald Oude Elferink
author_facet Jacqueline Langedijk
Ruth Bolier
Dagmar Tolenaars
Lysbeth ten Bloemendaal
Suzanne Duijst
Dirk de Waart
Ulrich Beuers
Piter Bosma
Ronald Oude Elferink
author_sort Jacqueline Langedijk
title Reduced spontaneous itch in mouse models of cholestasis
title_short Reduced spontaneous itch in mouse models of cholestasis
title_full Reduced spontaneous itch in mouse models of cholestasis
title_fullStr Reduced spontaneous itch in mouse models of cholestasis
title_full_unstemmed Reduced spontaneous itch in mouse models of cholestasis
title_sort reduced spontaneous itch in mouse models of cholestasis
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/8a91086451c548c488f3ed16188f6c17
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