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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Moriarty, Miriam A. Ryan, Rebecca Lalor, Pierce Dockery, Peter Byrnes, Lucy Grealy, Maura |
| Description | Country affiliation: Ireland Author Affiliation: Moriarty MA ( Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland.) |
| Abstract | The desmosomal armadillo protein plakophilin 2 is the only plakophilin expressed in the heart, and mutations in the human plakophilin 2 gene result in arrhythmogenic right ventricular cardiomyopathy. To investigate loss of function, we knocked down plakophilin 2 by morpholino microinjection in zebrafish. This resulted in decreased heart rate, cardiac oedema, blood pooling, a failure of the heart to pattern correctly and a twisted tail. Co-injection of plakophilin 2 mRNA rescued the morphant phenotype, indicating the specificity of the knockdown. Desmosome numbers were decreased in morphant hearts and the plaque and midline structures of the desmosomes in the intercalated discs were disrupted when examined by electron microscopy. cmlc2 and vmhc expression at 48 hours post-fertilization (hpf) showed incomplete looping of the heart in morphant embryos by whole mount in situ hybridization, and bmp4 expression was expanded into the ventricle. The domain of expression of the heart marker nkx2.5 at 24 hpf was expanded. At the 18 somite stage, expression of the cardiogenic gene lefty2 was abolished in the left cardiac field, with concomitant increases in bmp4, spaw and lefty1 expression, likely resulting in the looping defects. These results indicate that plakophilin 2 has both structural and signalling roles in zebrafish heart development. |
| File Format | HTM / HTML |
| ISSN | 02146282 |
| e-ISSN | 16963547 |
| Journal | The International Journal of Developmental Biology |
| Issue Number | 9 |
| Volume Number | 56 |
| Language | English |
| Publisher | University of the Basque Country Press |
| Publisher Date | 2012-01-01 |
| Publisher Place | Spain |
| Access Restriction | Open |
| Subject Keyword | Discipline Embryology Discipline Biology Embryo, Nonmammalian Metabolism Heart Rate Genetics Heart Embryology Organogenesis Plakophilins Zebrafish Animals Bone Morphogenetic Protein 4 Left-right Determination Factors Myocardium Phenotype Zebrafish Proteins Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Developmental Biology Embryology |
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