title: Characterization and in vivo functional analysis of splice variants of cypher.
abstract: Previously, we reported two splice variants of Cypher, a striated muscle-specific PDZLIM domain protein, Cypher1 and Cypher2. We have now characterized four additional splice isoforms, two of which are novel. The six isoforms can be divided into skeletal or cardiac specific classes, based on the inclusion of skeletal or cardiac specific domains. Short and long isoforms share an N-terminal PDZ domain, but the three C-terminal LIM domains are unique to long isoforms. By RNA and protein analysis, we have demonstrated that Cypher isoforms are developmentally regulated in both skeletal and cardiac muscle. We have previously shown that knockout of Cypher is neonatal lethal. To investigate the function of splice variants in vivo, we have performed a rescue experiment of the Cypher null mutant by replacing the endogenous Cypher gene with cDNAs encoding either a short or long skeletal muscle isoform. In contrast to Cypher null mice, a percentage of mice that express only a short or a long skeletal muscle-specific isoform can survive to at least 1 year of age. Although surviving mice exhibit muscle pathology, these results suggest that either isoform is sufficient to rescue the lethality associated with the absence of Cypher.
authors.affiliation: Institute of Molecular Medicine and Department of Medicine, University of California at San Diego, School of Medicine, La Jolla, California 92093-0641, USA.
authors.forename: Chengqun
authors.initials: C
authors.lastname: Huang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.forename: Peihua
authors.initials: P
authors.lastname: Liang
authors.forename: Melinda S
authors.initials: MS
authors.lastname: Hollander
authors.forename: Farah
authors.initials: F
authors.lastname: Sheikh
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Marion
authors.initials: M
authors.lastname: Greaser
authors.forename: G Diane
authors.initials: GD
authors.lastname: Shelton
authors.forename: Sylvia
authors.initials: S
authors.lastname: Evans
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins; D002470:Cell Survival; D018076:DNA, Complementary / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins; D006720:Homozygote; D060588:LIM Domain Proteins; D051379:Mice; D008957:Models, Genetic; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010641:Phenotype; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; C485639:Ldb3 protein, mouse; D009124:Muscle Proteins; D020033:Protein Isoforms; D012313:RNA