Leiden Muscular Dystrophy pages

Utrophin (UTRN)

(last modified November 2003, 2003)



Contents




Summary


NOTE: the data regarding utrophin displayed at these pages are far from complete.

Utrophin, originally described as DMD-like (DMDL) or dystrophin-related protein (DRP), was discovered by Love et al. upon screening cDNA-libraries with a fragment containing the C-terminal domain of dystrophin. The name 'utrophin', for ubiquitous dystrophin, was introduced later by Blake et al. The utrophin gene, (Gene Symbol UTRN, aliases DMDL, DRP, DRP1) maps to the long arm of chromosome 6 (6q24, mouse chromosome 10) and measures about 900 kb (Pearce). The structure of the gene bears large similarities to that of the dystrophin gene. In adult tissues, utrophin RNA is found abundantly in lung but also in muscle, brain, kidney, liver, spleen and stomach. Utrophin is alternatively spliced and widely expressed in cultured cells, including mouse ES-cells (Tinsley). Utrophin contains an actin-binding N-terminus, a triple coiled-coil repeat central region, and a C-terminus that consists of protein-protein interaction motifs which interact with dystroglycan protein components. In normal adult muscle, utrophin is located at the neuromuscular synapse and myotendinous junctions, where it participates in post-synaptic membrane maintenance and acetylcholine receptor clustering (Nguyen thi Man). In muscles of DMD-patients and female DMD-carriers, utrophin protein expression, found in dystrophin-negative fibers only, is dramatically increased. During human fetal muscle development, utrophin is found at the sarcolemma before dystrophin is expressed. Once dystrophin is expressed, utrophin disappears from the membrane. No reports have yet associated mutations in the utrophin gene with disease. Mouse studies suggest that this gene may serve as a functional substitute for the dystrophin gene and therefore, may serve as a potential therapeutic alternative to muscular dystrophy caused by mutations in the dystrophin gene.


The utrophin gene


Links to other databases:
Gene Symbol nomenclature   LocusLink   OMIM Gene Map    GDB

Utrophin, originally described as DMD-like (DMDL) or dystrophin-related protein (DRP), was discovered by Love et al. upon screening cDNA-libraries with a fragment containing the C-terminal domain of dystrophin. One positive clone was isolated which contained a different but homologous sequence (65% identity at the nucleotide level). The mRNA was estimated to measure 13 kb and was found to be expressed in cultured human fetal muscle cells, adult skeletal muscle and gut (smooth muscle). The name 'utrophin', for ubiquitous dystrophin, was introduced later by Blake et al.

The utrophin gene, (Gene Symbol UTRN, aliases DMDL, DRP, DRP1) maps to the long arm of chromosome 6 (6q24) and measures about 900 kb (Pearce). The structure of the gene bears large similarities to that of the dystrophin gene. In contrast to dystrophin, the utrophin gene has a long 5' untranslated region, split over two exons, and it is preceeded by an HTF-island. In mouse, the gene maps to chromosome 10.

Exon Exon size (bp) Intron size (kb) 5' cDNA position Splice after Remarks
1         5'UTR
2         5'UTR / .. bp coding

Legend:
Exon: numbering of exons and intron/exon boundaries are according to ..., with the first base of the Met-codon counted as position 1 (see ...reference sequence). Exon size: size of exon indicated in basepairs. Intron size: size of intron indicated in kilobasepairs. 5' cDNA position: first base of the exon (according to cDNA sequence ...). Splice after: splicing occurs in between of two coding triplets (0), after the first (1) or the second (2) base of a triplet. Remarks: 5'UTR = 5' untranslated region, 3"UTR = 3' untranslated region.


The utrophin RNA


Links to other databases:  UniGene - Hs.17401

Utrophin is ubiquituously expressed. In adult tissues, it is found abundantly in lung but also in muscle, brain, kidney, liver, spleen and stomach. Utrophin is also widely expressed in cultured cells, including mouse ES-cells (Tinsley). Alternative splicing of the utrophin gene has been described but the transcripts have not yet been characterized.


The utrophin protein


Utrophin shares both structural and functional similarities with dystrophin. Utrophin contains an actin-binding N-terminus, a triple coiled-coil repeat central region, and a C-terminus that consists of protein-protein interaction motifs which interact with dystroglycan protein components.

In normal adult muscle, utrophin is located at the neuromuscular synapse and myotendinous junctions, where it participates in post-synaptic membrane maintenance and acetylcholine receptor clustering (Nguyen thi Man). In muscles of DMD-patients and female DMD-carriers, utrophin protein expression, found in dystrophin-negative fibers only, is dramatically increased. During human fetal muscle development, utrophin is found at the sarcolemma before dystrophin is expressed. Once dystrophin is expressed, utrophin disappears from the membrane.

utrophin antibodies

Similarity to other proteins

Over its full lenght, utrophin is homologous to dystrophin. Homology varies from 85% (identity 73%) for the actin binding domain to less than 30% in regions of the central rod domain.


Utrophin and disease


Links to other databases:   OMIM: 128240

No reports have yet associated mutations in the utrophin gene with disease.

Animal models

Mouse studies suggest that this gene may serve as a functional substitute for the dystrophin gene and therefore,
may serve as a potential therapeutic alternative to muscular dystrophy caused by mutations in the dystrophin gene.


Miscelanneous


DNA-primers:

Amplified Length Reference forward primer reverse primer Name
exon 1          

Legend:
Exonic sequences are in upper case, intronic and gene flanking sequences in lower case and added primer tails in italics. Amplified: region amplified. Numbering of exons is according to .... Length: length of PCR-product in basepairs. Reference: publication describing the primer(s). Forward primer: sequence of forward primer. Reverse primer: sequence of reverse primer. Name: name of the primers.


RNA-primers:

Amplified Length Reference Forward primer Reverse primer Name
           

Legend:
Exonic sequences are in upper case, intronic and gene flanking sequences in lower case and added primer tails in italics. Amplified: region amplified. Numbering of exons is according to .... Length: length of PCR-product in basepairs. Reference: publication describing the primer(s). Forward primer: sequence of forward primer. Reverse primer: sequence of reverse primer. Name: name of the primers.


Utrophin sequences




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