Deletion of Galgt2 (B4Galnt2) Reduces Muscle Growth in Response to Acute Injury and Increases Muscle Inflammation and Pathology in Dystrophin-Deficient Mice

Rui Xu, Neha Singhal, Yelda Serinagaoglu, Kumaran Chandrasekharan, Mandar Joshi, John A. Bauer, Paulus M.L. Janssen, Paul T. Martin

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2-/-mdx). Galgt2-/- mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdx mice.

Original languageEnglish
Article number2109
Pages (from-to)2668-2684
Number of pages17
JournalAmerican Journal of Pathology
Volume185
Issue number10
DOIs
StatePublished - Oct 2015

Bibliographical note

Funding Information:
Supported by NIH grant R01 AR049722 (P.T.M.). Muscle physiology experiments were partially supported by NIH grant P30 NS045758 (Core D support to P.M.L.J.).

Publisher Copyright:
© 2015 American Society for Investigative Pathology.

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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