title: Altered MEF2 isoforms in myotonic dystrophy and other neuromuscular disorders.
abstract: Because of their central role in muscle development and maintenance, MEF2 family members represent excellent candidate effectors of the muscle pathology in myotonic dystrophy (DM). We investigated the expression and alternative splicing of all four MEF2 genes in muscle from neuromuscular disorder (NMD) patients, including DM1 and DM2. We observed MEF2A and MEF2C overexpression in all NMD muscle, including 12 MEF2-interacting genes. Exon 4 and 5 usage in MEF2A and MEF2C was different between DM and normal muscle, with DM showing the embryonic isoform. Similar splicing differences were observed in other NMD muscle. For MEF2C, missplicing was more pronounced in DM than in other dystrophies. Our data confirm dysregulation of MEF2A and MEF2C expression and splicing in several NMD, including DM. Our findings demonstrate that aberrant splicing in NMD is independent from expression of mutant repeats, and suggests that some aberrant splicing, even in DM, may be compensatory rather than primary.
authors.affiliation: Department of Genetics, M.D. Anderson Cancer Center, Unit 1010, University of Texas, 1515 Holcombe Boulevard, Houston, Texas 77030-4009, USA.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Bachinski
authors.forename: Mario
authors.initials: M
authors.lastname: Sirito
authors.forename: Maria
authors.initials: M
authors.lastname: Böhme
authors.forename: Keith A
authors.initials: KA
authors.lastname: Baggerly
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
authors.forename: Ralf
authors.initials: R
authors.lastname: Krahe
mesh_terms: D015870:Gene Expression; D006801:Humans; D026161:MADS Domain Proteins / Q000235:genetics* / Q000378:metabolism; D064326:MEF2 Transcription Factors; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D009224:Myotonia Congenita / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
chemical_list: D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; C578040:MEF2C protein, human; D018006:Myogenic Regulatory Factors; D020033:Protein Isoforms