PROBLEM TO BE SOLVED: To provide a method for rendering cells hypermutable, and hypermutable cell lines altered genetically and phenotypically.SOLUTION: The invention relates to use of dominant negative alleles of human mismatch repair genes to generate hypermutable cells and organisms the use of introducing genes into cells and transgenic animals by which new cell lines and animal varieties with new and useful properties can be prepared more efficiently than by relying on the natural rate of mutation and use of mutagens for enhancing a rate of further augmented mutation.