Purification of dystrophin‐related protein (utrophin) from lung and its identification in pulmonary artery endothelial cells

Matsumura, Kiichiro; Shasby, D. Michael; Campbell, Kevin P.

doi:10.1016/0014-5793(93)81810-m

Cited by 35 publications

(13 citation statements)

References 35 publications

(46 reference statements)

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“…A). Postnatal Utrn is most abundant in lung total Utrn ‐A and Utrn ‐B mRNA levels agree with prior studies ; and low levels of Utrn‐C, D and F (Fig. A, Table S2) are comparable with wild‐type mRNA profiles.…”

Section: Resultssupporting

confidence: 89%

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

Perkins

Davies

2018

FEBS Letters

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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.

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Section: Resultssupporting

confidence: 89%

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

Perkins

Davies

2018

FEBS Letters

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“…The expression of utrophin in vascular endothelium has previously been recognized (33); the finding that the B-isoform is specific for this structure suggests that it may have an important endothelial function. Mice lacking utrophin have abnormal NMJs; other gross pathology has not been identified, but it is possible that a subtle phenotype results from defects of endothelial function (29,34).…”

Section: A-utrophin Up-regulation In Skeletal and Cardiac Muscle Is Nmentioning

confidence: 99%

A- and B-utrophin Have Different Expression Patterns and Are Differentially Up-regulated in mdx Muscle

Weir¹,

Burton

Harrod

et al. 2002

Journal of Biological Chemistry

117

110

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Duchenne muscular dystrophy (DMD) is a fatal childhood disease caused by mutations that abolish the expression of dystrophin in muscle. Utrophin is a paralogue of dystrophin and can functionally replace it in skeletal muscle. A method to induce utrophin up-regulation in muscle should therefore be therapeutically useful in DMD. We have previously shown that there are two full-length utrophin mRNA species: A and B. Here we describe the generation and characterization of antibodies specific to A-and B-utrophin. We show that both mRNA isoforms are translated into full-length proteins, which have very different expression patterns. B-utrophin is expressed in vascular endothelial cells; A-utrophin is expressed at the neuromuscular junction, choroid plexus, pia mater, and renal glomerulus. We have analyzed the expression of A-and B-utrophin protein and RNA in dystrophin-deficient tissues. We conclude that (i) the previously described expression patterns of utrophin represent a composite of A-and B-utrophin, (ii) A-but not B-utrophin is up-regulated in dystrophin-deficient striated muscle, and (iii) this upregulation occurs post-transcriptionally with an additional transcriptional component in skeletal muscle. These results have important implications for understanding the biology of utrophin and are crucial for future studies aiming to effect its therapeutic up-regulation in DMD patients.

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“…Utrophin is found in many other tissues in addition to muscle; for example, it occurs at significant levels in smooth muscle and is relatively abundant in adult lung and intestine (8,9). In the brain utrophin is found in the astroglia surrounding the brain capillaries (10), and it is also expressed in cultured schwannoma and glial cells (8,11).…”

mentioning

confidence: 99%

G-utrophin, the autosomal homologue of dystrophin Dp116, is expressed in sensory ganglia and brain.

Blake

Schofield

Zuellig

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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The utrophin gene is closely related to the dystrophin gene in both sequence and genomic structure. The Duchenne muscular dystrophy (DMD) locus encodes three 14-kb dystrophin transcripts in addition to several smaller isoforms, one of which, Dpll6, is specific to peripheral nerve. We describe here the corresponding 5.5-kb mRNA from the utrophin locus. This transcript, designated G-utrophin, is of particular interest because it is specifically expressed in the adult mouse brain and appears to be the predominant utrophin transcript in this tissue. G-utrophin is expressed in brain sites generally different from the regions expressing 18-dystroglycan. During mouse embryogenesis G-utrophin is also seen in the developing sensory ganglia. Our data confirm the close evolutionary relationships between the DMD and utrophin loci; however, the functions for the corresponding proteins probably differ.

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Purification of dystrophin‐related protein (utrophin) from lung and its identification in pulmonary artery endothelial cells

Cited by 35 publications

References 35 publications

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

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

A- and B-utrophin Have Different Expression Patterns and Are Differentially Up-regulated in mdx Muscle

G-utrophin, the autosomal homologue of dystrophin Dp116, is expressed in sensory ganglia and brain.

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