Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair.
Proc Natl Acad Sci U S A
; 111(16): 6004-9, 2014 Apr 22.
Article
em En
| MEDLINE
| ID: mdl-24717843
ABSTRACT
Many monogenic disorders, including the muscular dystrophies, display phenotypic variability despite the same disease-causing mutation. To identify genetic modifiers of muscular dystrophy and its associated cardiomyopathy, we used quantitative trait locus mapping and whole genome sequencing in a mouse model. This approach uncovered a modifier locus on chromosome 11 associated with sarcolemmal membrane damage and heart mass. Whole genome and RNA sequencing identified Anxa6, encoding annexin A6, as a modifier gene. A synonymous variant in exon 11 creates a cryptic splice donor, resulting in a truncated annexin A6 protein called ANXA6N32. Live cell imaging showed that annexin A6 orchestrates a repair zone and cap at the site of membrane disruption. In contrast, ANXA6N32 dramatically disrupted the annexin A6-rich cap and the associated repair zone, permitting membrane leak. Anxa6 is a modifier of muscular dystrophy and membrane repair after injury.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Sarcolema
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Cicatrização
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Anexina A6
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Distrofia Muscular Animal
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article