Genomic instability in Gadd45a-deficient mice

Gadd45a-null mice generated by gene targeting exhibited several of the phen otypes characteristic of p53-deficient mice, including genomic instability, increased radiation carcinogenesis and a low frequency of exencephaly. Gen omic instability was exemplified by aneuploidy, chromosome aberrations, gen e amplification and centrosome amplification, and was accompanied by abnorm alities in mitosis, cytokinesis and growth control. Unequal segregation of chromosomes due to multiple spindle poles during mitosis occurred in severa l Gadd45a(-/-) cell lineages and may contribute to the aneuploidy. Our resu lts indicate that Gadd45a is one component of the p53 pathway that contribu tes to the maintenance of genomic stability.