Patent ID: 8071838

Claim:
A method of identifying a gene and genetic mutation affecting cellular regeneration in a transgenic fish, the method comprising a) creating at least one mutation in a transgenic fish selected from the group consisting of a transgenic zebrafish and a transgenic medaka, wherein the genome of the transgenic fish comprises a transgene comprising a gene encoding i) an ablation promoting moiety; or ii) a coupled expression system consisting of an ablation promoting moiety and a cellular reporter protein that facilitates detection of cells expressing the transgene, wherein the ablation promoting moiety comprises at least one component of a pro-drug conversion system, wherein the gene is operably linked to a regulatory DNA sequence including at least a promoter element that regulates the expression of the gene such that the gene is expressed in a reproducible spatial and temporal pattern in the transgenic fish; b) subjecting mutant transgenic progeny of the mutant transgenic fish of step a and wildtype sibling transgenic progeny to targeted or regional cellular ablation within the context of a â€œforward geneticsâ€ mutagenesis screen; and c) identifying mutation(s) affecting cellular regeneration by identifying mutant transgenic progeny with an alteration in competency or deficiency for cellular regeneration as compared to wildtype sibling transgenic progeny, wherein the alteration is detected as a difference between mutant transgenic progeny and wildtype sibling transgenic progeny in a presence or an absence of regenerating cells and/or as a difference between mutant transgenic progeny and wildtype sibling transgenic progeny in a presence or an absence of the cellular reporter protein in regenerating cells, whereby instances of altered regenerative capacity are due to a mutation(s) that causes an alteration in gene structure, gene product structure, gene product function, and/or gene product expression, thereby identifying the mutant gene and/or gene product as a factor capable of influencing the process of cellular regeneration; and whereby mapping, cloning, and sequencing of the gene identifies the genetic mutation affecting cellular regeneration in a transgenic fish.