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Human Molecular Genetics, 2002, Vol. 11, No. 7 805-814
© 2002 Oxford University Press

Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells

Majid Fardaei, Mark T. Rogers1, Helena M. Thorpe, Kenneth Larkin, Marion G. Hamshere2, Peter S. Harper1 and J. David Brook+

Institute of Genetics, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK, 1Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK and 2School of Life and Environmental Sciences, University of Nottingham, Biological Sciences Building, University Park, Nottingham NG7 2RD, UK

Myotonic dystrophy is a complex neuromuscular disorder associated with DNA expansion mutations in two different genes. In DM1 a CTG repeat in the 3'-untranslated region of DMPK is expanded, whereas in DM2 an intronic CCTG expansion occurs in the gene ZNF9. Transcripts containing expanded repeats form foci in the nuclei of DM1 and DM2 cells. Recent work using antibodies has shown that proteins related to Drosophila muscleblind co-localize with repeat foci in DM1 and DM2 cells. We show that rather than there being a single human muscleblind gene producing multiple proteins through alternative splicing, there are in fact three different muscleblind genes, MBNL, MBLL and MBXL, which map to chromosomes 3, 13 and X, respectively, and which show extensive alternative splicing. Two of the genes, MBNL and MBLL, are expressed in many adult tissues whereas MBXL is expressed predominantly in the placenta. Green fluorescent protein-tagged versions of MBNL, MBLL and MBXL co-localize with nuclear foci in DM1 and DM2 cells, suggesting that all three proteins may play a role in DM pathophysiology.

+ To whom correspondence should be addressed. Tel: +44 115 8493217; Fax: +44 115 9709906; Email: david.brook@nottingham.ac.uk


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