In mouse primary tail fibroblasts, the K577M-WRNp was localized to nucleoplasm which is different from human WRNp. There is no correlation between 4-nitroquinoline-1-oxide (4NQO) sensitivity in the K577M-WRNp mouse primary tail fibroblasts. There is significant reduction in survival of the K577M-WRNp cells. The replicative potentials of the K577M-WRNp cell populations are significantly decreased and the overexpression of K577M-WRNp reduced the expression of the endogenous mouse WRN protein. This dominant-negative mutant protein may form multimeric complexes that disrupt the overall function of the helicase activity. The aging phenotype is under investigation.