Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair

Kayleigh A. Swaggart, Alexis R. Demonbreun, Andy H. Vo, Kaitlin E. Swanson, Ellis Y. Kim, John P. Fahrenbach, Jenan Holley-Cuthrell, Ascia Eskin, Zugen Chen, Kevin Squire, Ahlke Heydemann, Abraham A. Palmer, Stanley F. Nelson, Elizabeth M. McNally*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)6004-6009
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
StatePublished - Apr 22 2014


  • Dystrophin
  • Muscle
  • Plasma membrane

ASJC Scopus subject areas

  • General

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