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Altered globotriaosylceramide accumulation and mucosal neuronal fiber density in the colon of the Fabry disease mouse model
Author(s) -
Masotti Martina,
Delprete Cecilia,
Dothel Giovanni,
Donadio Vincenzo,
Rimondini Roberto,
Politei Juan Manuel,
Liguori Rocco,
Caprini Marco
Publication year - 2019
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13529
Subject(s) - globotriaosylceramide , fabry disease , gastrointestinal tract , myenteric plexus , pathophysiology , pathology , enteric nervous system , knockout mouse , biology , disease , medicine , immunohistochemistry , endocrinology , receptor
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.