Using a zebrafish Danio rerio model system to study NOTCH1-induced T-cell leukaemia
Notch receptors are a family of cell-surface proteins that regulate cell fate decisions and growth control. Human NOTCH1 gain-of-function mutations–deletions have been found in c. 60% of patients with T-cell acute lymphoblastic leukaemia (T-ALL). Therefore, understanding the molecular mechanisms by which dysregulated Notch-signalling induces leukaemia is of importance and may reveal novel targets for the development of more effective therapies. Zebrafish, Danio rerio, is an ideal model system to use for forward genetic screens to uncover pathways critical for transformation. Danio rerio also have the capacity for small molecule screening for drug discovery. rag2-ICN1-EGFP transgenic fish have been created that develop a T-cell leukaemia, and these fish are now being used in genetic modifier screens.