Identification and analysis of zebrafish models of eterotaxy syndrome

Doctor's Name: 
Alvin Chin, MD
Children's Hospital of Philadelphia

This is a genetic study on the development of congenital heart defects in association with heterotaxy syndrome. Heterotaxy syndrome involves abnormal organ placement in the body, including the heart. Often times, the liver is in the midline, the stomach and heart may be on the right side, and the splenic tissue may be multiple (polysplenia syndrome) or absent (asplenia syndrome). The congenital heart disease associated with heterotaxy is usually severe and is associated with high infant and childhood mortality. This study uses zebrafish embryo since it is transparent and organ placement in the embryo is readily identifiable. Furthermore, the zebrafish embryonic heart segments are similar to mammalian embryonic heart segments.

This study has three specific aims. The first aim is to determine whether a specific genetic region, the embryonic shield (or "organizer") region, is necessary and sufficient to specify left-right polarity in the embryo. The second aim is to determine whether the notochord (the future brain and spinal column) that runs down the midline of the embryo is involved in the translation of left-right organ polarity. Finally, screening will be performed on novel mutations that produce abnormalities in left-right polarity. By characterizing the genetic pathway in detail, this will hopefully yield insight into the development of heterotaxy syndrome in the human, and in turn, potentially lead to ways to decrease or eliminate the high mortality that patients with this syndrome presently have.

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