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Zebrafish (Danio rerio) are fresh water tropical fish which can produce hundreds of eggs at once. Zebrafish are excellent research models, as fertilisation and development occur externally and embryos are transparent, allowing easy visualisation and experimental manipulation during development.

Zebrafish brains are comparable to that of humans, and the zebrafish genome has been sequenced by the Sanger Centre, meaning that some of the genetic mutations mistakes or responsible for human disease can be studied in the zebrafish. Developing zebrafish can also be used as platform for drug discovery due to their easy absorption of compounds in water and their very small size. Large scale drug screening in zebrafish could lead to promising compounds being identified for further testing in mouse models.

Some NCL genes have been knocked-down in the zebrafish, including CLN2, CLN7, CLN10 and CLN11 disease. This means that the relevant protein will not be produced and, the  future contribution of the zebrafish model to NCL research, will depend on the likeness of each knock-down to each type of NCL. For example, the tpp1sa1 zebrafish is highly suitable for CLN2 disease modelling and experimental therapy testing, as it represents the symptoms and relative time course of CLN2 disease in humans.

However, there are still some aspects of the disease that remain to be modelled, such as lipofuscin (storage material) accumulation. Knockdown of Cathepsin D, the protein deficient in CLN10 disease, revealed defects in the zebrafish eye that could provide avenues for study in the mouse.

Gini Brickell MSc

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