Reduced spontaneous itch in mouse models of cholestasis.
Jacqueline LangedijkRuth BolierDagmar TolenaarsLysbeth Ten BloemendaalSuzanne DuijstDirk de WaartUlrich BeuersPiter BosmaRonald P Oude ElferinkPublished in: Scientific reports (2021)
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.
Keyphrases
- wild type
- high fat diet induced
- liver injury
- drug induced
- end stage renal disease
- multiple sclerosis
- type diabetes
- newly diagnosed
- insulin resistance
- chronic kidney disease
- liver fibrosis
- computed tomography
- atopic dermatitis
- cell proliferation
- transcription factor
- early onset
- peritoneal dialysis
- patient reported outcomes