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Zebrafish: A model organism amenable to mechanistic interrogation

We are currently utilizing a broad range of approaches to integrate biochemical and biophysical perspective in the test tube with whole animal physiology using zebrafish. Our work on molecular chaperones has recently evolved from a historical focus on biophysical studies in the test tube to testing hypotheses in-vivo using knockout and transgenic strategies in the zebrafish. This new direction is taking on a definitely more cell biology and physiology perspectives. Zebrafish (zf) has emerged as a powerful model system for investigation of the  physiological roles of proteins particularity following spectacular advances in its genetic manipulation ushered in by CRISPR-Cas9.  Compared to the mouse, zf husbandry is easy and less expensive. The embryos are extracorporeal and transparent during the first few days of their development allowing for the application of imaging approaches.

In a recent paper, we have shown that the loss of the small heat-shock protein, αB-crystallin, compromises the stress resistance of the heart. Below we illustrate the power of zebrafish with an in vivo recording of the heart beating of a 4dpf Cryabb-/- embryos treated with dexamethasone, showing arrhythmic heartbeats as well as severe pericardial edema (10 frames per second; movie total length: 44 sec).