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Alterations in the AKT/mTOR pathway in dystroglycanopathy muscle
Author(s) -
Foltz Steven J,
Beedle Aaron M
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1199.4
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , biology , microbiology and biotechnology , phenotype , signal transduction , conditional gene knockout , skeletal muscle , phosphorylation , cancer research , gene , endocrinology , genetics
Secondary dystroglycanopathies are a subset of muscular dystrophies caused by aberrant glycosylation of α‐Dystroglycan (DG). Hypoglycosylated αDG is unable to bind to its extracellular targets, disrupting a crucial link between the extracellular basement membrane and the intracellular cytoskeleton. FKTN , encoding fukutin, is one of several genes identified as causative for dystroglycanopathy. Similar to human patients, skeletal muscle from conditional fukutin KO mice shows a progressive dystrophic phenotype. The objective of our study is to characterize alterations in cellular signaling pathways in dystroglycanopathy disease using a conditional Fktn knockout mouse model. Using techniques to monitor gene expression, protein expression and protein phosphorylation, we find that there are alterations in multiple factors in the PI3K/AKT/mTOR signaling cascade in young Fktn KO mice. Furthermore, preliminary data suggest a differential response to pharmacological inhibition of this pathway between KO mice and age‐matched littermate controls. Our findings indicate that changes in the AKT/mTOR signaling pathway are present in young Fktn KO mice, but the precise role of AKT/mTOR signaling in dystroglycanopathy muscle requires further clarification. Research supported by the University of Georgia College of Pharmacy.