Alternative utrophin mRNAs contribute to phenotypic differences between dystrophin-deficient mice and Duchenne muscular dystrophy.

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Perkins KJ,Davies KE

doi

10.1002/1873-3468.13099

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

1856-1869

issue

11

eissn

0014-5793

issn

1873-3468

journal_volume

592

pub_type

信件
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