Genetically-accurate models of CLN3 disease are needed to develop personalised medicine. This project will use antisense morpholinos and CLN3 mRNA injection in zebrafish to model the common 1kb deletion seen in most CLN3 disease patients, other CLN3 point mutations, and CLN3 knockout. Our data indicates that the 1kb deletion results in altered and partial loss of function. Genetic accuracy of the zebrafish models will be determined by CLN3 mRNA analysis, and phenotypic accuracy by global RNA analysis and phenotypic analysis. The project will establish the functions of the 1kb deletion mutation compared to knock-out and point mutations, informing therapeutic development.
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