Expression of four alternative dystrophin transcripts in brain regions regulated by different promoters

Cognitive impairment occurs in one-third of patients with Duchenne muscular dystrophy, a lethal X-linked, recessive disease caused by mutations in the dystrophin gene which is expressed in both brain and muscle, the two transcripts having alternative first exons. Previous reports have indicated that...

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Bibliographic Details
Published in:Human molecular genetics 1992-10, Vol.1 (7), p.505-510
Main Authors: Górecki, Dariusz C., Monaco, Anthony P., Derry, Jonathan M. J., Walker, Ann P., Barnard, Eric A., Barnard, Pene J.
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Biological and medical sciences
brain
Brain - metabolism
Diseases of striated muscles. Neuromuscular diseases
DNA
DNA Probes
Duchenne's muscular dystrophy
dystrophin
Dystrophin - genetics
expression
Humans
In Situ Hybridization
man
Medical sciences
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Neurology
Polymerase Chain Reaction
Promoter Regions, Genetic
promoters
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Sequence Alignment
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Summary:Cognitive impairment occurs in one-third of patients with Duchenne muscular dystrophy, a lethal X-linked, recessive disease caused by mutations in the dystrophin gene which is expressed in both brain and muscle, the two transcripts having alternative first exons. Previous reports have indicated that the ‘brain-type’ dystrophin transcript predominates in brain. Using in situ hybridisation with antisense oligonucleotides, expression of four distinct mRNAs in specific brain areas is demonstrated here; the 14 kb muscle-type and brain-type transcripts were found to coexist in cortical and hippocampal neurons and two new transcripts have been identified in dentate gyrus and cerebellar Purkinje neurons, respectively. The latter has a novel first exon which was isolated and sequenced from mouse and human, and which would encode a protein with a different amino-terminus from the known muscle- and brain-type isoforms. Mapping in human located this exon in a large intron between the muscle-type promoter and second exon of the dystrophin gene. This finding of four alternative transcripts regulated by different promoters in brain reveals a new complexity to dystrophin expression that may have important insights for mental retardation mechanisms.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/1.7.505