The Popeye domain containing (Popdc) genes encode a family of transmembrane proteins with an evolutionary conserved Popeye domain, which functions as a cAMP-binding domain. Analysis of Popdc1 and Popdc2 null mutants in mice revealed that the Popdc family of genes might play a role in age-related sinus node degeneration that consequently leads to progressive bradyarrythmia phenotypes under stress. To advance our understanding of the role of Popdc genes in the cardiac conduction system (CCS), we performed morpholino-mediated knockdown experiments in zebrafish, capitalising on its fast development and comparable electrophysiology with humans, among other merits as a model for cardiovascular studies. Upon knockdown of popdc2, aberrant development of heart and skeletal muscle was observed. The morphant hearts were morphologically distorted in addition to massive oedema which confounded analysis of CCS function. A submaximal dose of morpholino that does not affect cardiac morphology was then used, which revealed the morphant cardiac arrhythmia phenotype, characterized by irregular ventricular contractions with a 2:1, or 3:1 atrial/ventricular conduction ratio. A reduction in heart frequency was also observed. Recordings of calcium transients in popdc2 morphants on the background of a transgenic calcium reporter line using high spatial resolution SPIM microscopy further detailed the spectrum of arrhythmic phenotypes. Ongoing analysis of the CCS phenotypes in popdc1 morphant suggests the presence of cardiac conduction disorders in the popdc1 morphant. These data suggest an important and evolutionary conserved role of the Popdc gene family in CCS function.
University of Manchester (2012) Proc Physiol Soc 28, C15 and PC15
Oral Communications: The Popeye domain containing gene family is required for cardiac conduction system development in zebrafish
K. L. Poon1, B. C. Kirchmaier2, T. Schwerte3, J. Huisken5, C. Winkler6, B. Jungblut7, D. Stainier5, P. Kohl4,8, T. A. Quinn4,8, T. Brand1
1. Developmental Dynamics, NHLI/Imperial College London, London, United Kingdom. 2. Hubrecht Laboratory, Institute for Developmental Biology, Utrecht, Netherlands. 3. Institute of Zoology, Innsbruck, Austria. 4. Cardiac Biophysics and Systems Biology, NHLI/Imperial College London, London, United Kingdom. 5. University of California San Francisco, San Francsico, California, United States. 6. Department of Biological Sciences, University of Singapore, Singapore, Singapore. 7. Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. 8. Department of Computer Science, University of Oxford, Oxford, United Kingdom.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.