Duchenne muscular dystrophy (DMD) is a fatal disorder caused by absence of functional dystrophin protein. Compensation in dystrophin-deficient (mdx) mice may be achieved by overexpression of its fetal paralogue, utrophin. Strategies to increase utrophin levels by stimulating promoter activity using small compounds are therefore a promising pharmacological approach. Here, we characterise similarities and differences existing within the mouse and human utrophin locus to assist in high-throughput screening for potential utrophin modulator drugs. We identified five novel 5'-utrophin isoforms (A',B',C,D and F) in adult and embryonic tissue. As the more efficient utrophin-based response in mdx skeletal muscle appears to involve independent transcriptional activation of conserved, myogenic isoforms (A' and F), elevating their paralogues in DMD patients is an encouraging therapeutic strategy. © 2018 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Kelly J Perkins, Kay E Davies. Alternative utrophin mRNAs contribute to phenotypic differences between dystrophin-deficient mice and Duchenne muscular dystrophy. FEBS letters. 2018 Jun;592(11):1856-1869
PMID: 29772070
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