Altered globotriaosylceramide accumulation and mucosal neuronal fiber density in the colon of the Fabry disease mouse model.
Neurogastroenterol Motil
; 31(3): e13529, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30609268
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. KEYRESULTS:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trihexosilceramidas
/
Enfermedad de Fabry
/
Colon
/
Fibras Nerviosas
Límite:
Animals
Idioma:
En
Revista:
Neurogastroenterol Motil
Asunto de la revista:
GASTROENTEROLOGIA
/
NEUROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Italia