Altered globotriaosylceramide accumulation and mucosal neuronal fiber density in the colon of the Fabry disease mouse model

Martina Masotti, Cecilia Delprete, Giovanni Dothel, Vincenzo Donadio, Roberto Rimondini, Juan Manuel Politei, Rocco Liguori, Marco Caprini

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Abstract

Background: Fabry disease (FD) is a hereditary X-linked metabolic storage disorder characterized by deficient or absent lysosomal α-galactosidase A (α-Gal A) activity. This deficiency causes progressive accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in nearly all organ systems. Gastrointestinal (GI) symptoms can be very debilitating and are among the most frequent and earliest of the disease. As the pathophysiology of these symptoms is poorly understood, we carried out a morphological and molecular characterization of the GI tract in α-Gal A knockout mice colon in order to reveal the underlying mechanisms. Methods: Here, we performed the first morphological and biomolecular characterization of the colon wall structure in the GI tract of the α-Gal A knock-out mouse (α-Gal A −/0), a murine model of FD. Key Results: Our data show a greater thickness of the gastrointestinal wall in α-Gal A (−/0) mice due to enlarged myenteric plexus' ganglia. This change is paralleled by a marked Gb3 accumulation in the gastrointestinal wall and a decreased and scattered pattern of mucosal nerve fibers. Conclusions and Inferences: The observed alterations are likely to be a leading cause of gut motor dysfunctions experienced by FD patients and imply that the α-Gal A (−/0) male mouse represents a reliable model for translational studies on enteropathic pain and GI symptoms in FD.

Original languageEnglish
Article numbere13529
JournalNeurogastroenterology and Motility
Volume31
Issue number3
DOIs
Publication statusPublished - Mar 1 2019

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Keywords

  • enteropathic pain
  • Fabry disease
  • gastrointestinal
  • neuronal fiber density
  • α-Gal A null mice

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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