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Author Notes:

Corresponding author at: University of Palermo, Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), Corso Tukory 129, 90134 Palermo, Italy. natale.belluardo@unipa.it (N. Belluardo).

Co-first authors: Zizzo MG, Finchi M

Co-senior authors: Belluardo N, Serio R

Zizzo MG, Frinchi M, Nuzzo D performed experiments.

Jinnah HA provided HGprt knock out mice and contributed to write the text.

Mudò G, Mulè F processed data.

Condorelli DF, Caciagli F, Ciccarelli R, Di Iorio P contributed to write the text.

Belluardo N, Serio R conceived and planned the work and contributed to write the text.

The authors declare that they have no conflicts of interest.


Research Funding:

This work was supported by grants from “Fondi Finanziamento della Ricerca (FFR)”, University of Palermo.

The work was supported in part by the National Institutes of Health in the USA (grant number R56 NS102980).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Lesch-Nyhan
  • HGprt enzyme
  • HGprt deficient mice
  • Gastrointestinal motility
  • Colon
  • Dopamine
  • Oxidative stress
  • Cytokines

Altered gastrointestinal motility in an animal model of Lesch-Nyhan disease

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Journal Title:

Autonomic Neuroscience: Basic and Clinical


Volume 210


, Pages 55-64

Type of Work:

Article | Post-print: After Peer Review


Mutations in the HGPRT1 gene, which encodes hypoxanthine-guanine phosphoribosyltransferase (HGprt), housekeeping enzyme responsible for recycling purines, lead to Lesch-Nyhan disease (LND). Clinical expression of LND indicates that HGprt deficiency has adverse effects on gastrointestinal motility. Therefore, we aimed to evaluate intestinal motility in HGprt knockout mice (HGprt¯). Spontaneous and neurally evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips of distal colon. HGprt¯ tissues showed a lower in amplitude spontaneous activity and atropine-sensitivity neural contraction compared to control mice. The responses to carbachol and to high KCl were reduced, demonstrating a widespread impairment of contractility. L-NAME was not able in the HGprt¯ tissues to restore the large amplitude contractile activity typical of control. In HGprt¯ colon, a reduced expression of dopaminergic D1 receptor was observed together with the loss of its tonic inhibitory activity present in control-mice. The analysis of inflammatory and oxidative stress in colonic tissue of HGprt¯ mice revealed a significant increase of lipid peroxidation associated with over production of oxygen free radicals. In conclusion, HGprt deficiency in mice is associated with a decrease in colon contractility, not dependent upon reduction of acetylcholine release from the myenteric plexus or hyperactivity of inhibitory signalling. By contrast the increased levels of oxidative stress could partially explain the reduced colon motility in HGprt¯ mice. Colonic dysmotility observed in HGprt¯ mice may mimic the gastrointestinal dysfunctions symptoms of human syndrome, providing a useful animal model to elucidate the pathophysiology of this problem in the LND.

Copyright information:

© 2017 Elsevier B.V.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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