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Cloning of the rat utrophin and characterization of an alternate transcript

Zuellig, Richard A., Blake, Derek J., Tinsley, Jonathon M. and Davies, Kay E. 1996. Cloning of the rat utrophin and characterization of an alternate transcript. Journal of Muscle Research and Cell Motility 17 (1) , p. 110.

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Abstract

Utrophin is an autosomal homologue of dystrophin. The dystrophin gene is located on the X-chromosome, and its product, dystrophin, is missing in muscle fibres of patients with Duchenne muscular dystrophy. The absence of dystrophin is probably the cause for this dystrophy. The gene for the human utrophin protein was cloned recently and the deduced amino acid sequence shows a significant similarity to dystrophin (Tinsley et al., Nature, 360, 591- 3, 1992). It has also a similar structure with four domains, the actin binding domain, the spectrin-like rod domain, the cysteine rich (CR) domain and the C-terminal (CT) domain. The actin binding and the CR-CT domains exhibit 85% amino acid sequence similarity between dystrophin and utrophin. With 60% similarity the rod domain is less conserved. A rat cDNA library was screened with probes originating from mouse utrophin cDNAs. Several positive clones were found and characterized. Three clones were found to overlap and to contain the whole coding region for the utrophin protein. The combined cDNA contains an open reading frame of 10 254 bp and encodes a protein of 3419 amino acids. The rat utrophin exhibits a high amino acid sequence similarity of 91% over the entire protein towards the human utrophin. Two further clones were characterized. They contain a beginning (1.8 kb) identical to the 5’ rat utrophin sequence while their ends (0.3 and 0.1 kb) are identical among themselves but different from the rat utrophin. Preliminary Northern blots and results from PCR reactions support the notion that these two clones represent a short alternative transcript of the rat utrophin Recently the finding of a small (62 kDa) protein was reported, which reacts with two monoclonal antibodies. The antibodies are directed against the Nterminus of the human utrophin, but they also recognize the rat/ mouse utrophin (Nguyen et al., FEBS Letts, 358, 262-6, 1995). The size of the protein and the tissue distribution would correlate with the results from the Northern blots.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Additional Information: Abstract presented at 24th European Muscle Conference, Florence, Italy, 13-16 September 1995.
Publisher: Springer Verlag
ISSN: 0142-4319
Last Modified: 04 Jun 2017 05:12
URI: http://orca-mwe.cf.ac.uk/id/eprint/49484

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