TY - JOUR
T1 - Human and murine dystrophin mRNA transcripts are differentially expressed during skeletal muscle, heart, and brain development
AU - Bies, Roger D.
AU - Phelps, Stephanie F.
AU - Cortez, M. Dolores
AU - Roberts, Robert
AU - Caskey, C. Thomas
AU - Chamberlain, Jeffrey S.
N1 - Funding Information:
RDB and MDC were supported by a Bugher Fellowship/ American Heart Association Grant for Molecular Biology of the Cardiovascular System. This work was supported by grants from the Muscular Dystrophy Association to JSC and to CTC, and by grant R01 AR40864 from the National Institutes of Health to JSC. CTC is a Howard Hughes Medical Institute Investigator.
PY - 1992/4/11
Y1 - 1992/4/11
N2 - Dystrophin transcripts were shown to be alternatively spliced in a pattern characteristic of both tissue type and developmental stage. Multiple novel spliced forms of dystrophin mRNA were identified in murine brain tissue, skeletal and cardiac muscle, diaphragm, and human cardiac Purkinje fibers. The transcript diversity was greatest in adult, non-skeletal muscle tissues. Sequence analysis revealed that four tandem exons of the murine gene are differentially spliced in at least 11 separate patterns to generate distinct isoforms. Two of these forms were observed in all tissues examined, while several others were uniquely observed in cardiac muscle and brain. Cardiac Purkinje fibers express an isoform primarily observed in brain tissue. Several spliced transcripts were observed only in postnatal development. Differential utilization of a fifth exon results in two mRNA splice forms that encode separate embryonic and adult C-termini of dystrophin. Comparison of murine with human dystrophin mRNAs showed that similar isoform expression patterns exist across species. These observations suggest that functionally distinct isoforms of the dystrophin protein are expressed in separate tissues and at different stages of development. These isoforms may be of significance in understanding the various tissue-specific effects produced by dystrophin gene mutations in Duchenne and Becker muscular dystrophy patients.
AB - Dystrophin transcripts were shown to be alternatively spliced in a pattern characteristic of both tissue type and developmental stage. Multiple novel spliced forms of dystrophin mRNA were identified in murine brain tissue, skeletal and cardiac muscle, diaphragm, and human cardiac Purkinje fibers. The transcript diversity was greatest in adult, non-skeletal muscle tissues. Sequence analysis revealed that four tandem exons of the murine gene are differentially spliced in at least 11 separate patterns to generate distinct isoforms. Two of these forms were observed in all tissues examined, while several others were uniquely observed in cardiac muscle and brain. Cardiac Purkinje fibers express an isoform primarily observed in brain tissue. Several spliced transcripts were observed only in postnatal development. Differential utilization of a fifth exon results in two mRNA splice forms that encode separate embryonic and adult C-termini of dystrophin. Comparison of murine with human dystrophin mRNAs showed that similar isoform expression patterns exist across species. These observations suggest that functionally distinct isoforms of the dystrophin protein are expressed in separate tissues and at different stages of development. These isoforms may be of significance in understanding the various tissue-specific effects produced by dystrophin gene mutations in Duchenne and Becker muscular dystrophy patients.
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U2 - 10.1093/nar/20.7.1725
DO - 10.1093/nar/20.7.1725
M3 - Article
C2 - 1579466
AN - SCOPUS:0026519484
SN - 0305-1048
VL - 20
SP - 1725
EP - 1731
JO - Nucleic acids research
JF - Nucleic acids research
IS - 7
ER -