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Sci Rep. 2017 Feb 14;7:42506. doi: 10.1038/srep42506.

Analysis of Craniocardiac Malformations in Xenopus using Optical Coherence Tomography.

Author information

1
Pediatric Genomics Discovery Program, Department of Pediatrics, Yale University, 333 Cedar Street, New Haven, CT 06510, USA.
2
Department of Medical Informatics, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany.
3
Department of Radiology and Biomedical Imaging, Department of Pediatrics, Yale University, 333 Cedar, Street New Haven, CT 06510, USA.
4
Department of Biomedical Engineering and Applied Physics, Yale University, 333 Cedar Street, New Haven, CT 06510, USA.
5
Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.

Abstract

Birth defects affect 3% of children in the United States. Among the birth defects, congenital heart disease and craniofacial malformations are major causes of mortality and morbidity. Unfortunately, the genetic mechanisms underlying craniocardiac malformations remain largely uncharacterized. To address this, human genomic studies are identifying sequence variations in patients, resulting in numerous candidate genes. However, the molecular mechanisms of pathogenesis for most candidate genes are unknown. Therefore, there is a need for functional analyses in rapid and efficient animal models of human disease. Here, we coupled the frog Xenopus tropicalis with Optical Coherence Tomography (OCT) to create a fast and efficient system for testing craniocardiac candidate genes. OCT can image cross-sections of microscopic structures in vivo at resolutions approaching histology. Here, we identify optimal OCT imaging planes to visualize and quantitate Xenopus heart and facial structures establishing normative data. Next we evaluate known human congenital heart diseases: cardiomyopathy and heterotaxy. Finally, we examine craniofacial defects by a known human teratogen, cyclopamine. We recapitulate human phenotypes readily and quantify the functional and structural defects. Using this approach, we can quickly test human craniocardiac candidate genes for phenocopy as a critical first step towards understanding disease mechanisms of the candidate genes.

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