A system including: (i) a methodology for targeted cellular ablation in
zebrafish; (ii) a methodology for regional cellular ablation in
zebrafish. These methodologies are used to identify genetic components
that regulate cellular regeneration and to identify drug compounds that
influence cellular regeneration for the purpose of developing therapies
for degenerative conditions. Transgenic zebrafish disclosed herein
contain transgenic constructs composed of: (i) cell and/or tissue-type
specific regulatory elements (e.g. promoter and/or enhancer regions)
which delimit expression of operably linked gene product(s) to discrete
cellular populations; (ii) a gene product that promotes cellular ablation
composed of a pro-drug conversion system capable of converting nontoxic
pro-drugs into cytotoxic drugs, which is expressed alone or in connection
with; (iii) a reporter gene product that allows selective detection of
cells expressing the reporter--both prior to (initial cells) and
following cellular ablation (regenerated cells). Here we describe genetic
delivery of a pro-drug converting system in order to enable targeted
cellular ablation in zebrafish. Transgenic zebrafish of this invention
provide a high-throughput system for genetic dissection of the process of
cellular regeneration and, compound screening for the discovery of drugs
capable of promoting cellular regeneration.