The missense mutation C667F in murine ß-dystroglycan causes embryonic lethality, myopathy and blood-brain barrier destabilization.
Dis Model Mech
; 17(6)2024 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-38616731
ABSTRACT
Dystroglycan (DG) is an extracellular matrix receptor consisting of an α- and a ß-DG subunit encoded by the DAG1 gene. The homozygous mutation (c.2006G>T, p.Cys669Phe) in ß-DG causes muscle-eye-brain disease with multicystic leukodystrophy in humans. In a mouse model of this primary dystroglycanopathy, approximately two-thirds of homozygous embryos fail to develop to term. Mutant mice that are born undergo a normal postnatal development but show a late-onset myopathy with partially penetrant histopathological changes and an impaired performance on an activity wheel. Their brains and eyes are structurally normal, but the localization of mutant ß-DG is altered in the glial perivascular end-feet, resulting in a perturbed protein composition of the blood-brain and blood-retina barrier. In addition, α- and ß-DG protein levels are significantly reduced in muscle and brain of mutant mice. Owing to the partially penetrant developmental phenotype of the C669F ß-DG mice, they represent a novel and highly valuable mouse model with which to study the molecular effects of ß-DG functional alterations both during embryogenesis and in mature muscle, brain and eye, and to gain insight into the pathogenesis of primary dystroglycanopathies.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Barrera Hematoencefálica
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Mutación Missense
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Distroglicanos
Límite:
Animals
Idioma:
En
Revista:
Dis Model Mech
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Dis. model. mech. (Print)
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Disease models & mechanisms (Online)
Asunto de la revista:
MEDICINA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania