Mouse cells with null p53 mutation have all p53 isoforms deleted and lose negative growth control.

Abstract

Embryonic mouse cells containing a disrupted p53 gene (-/-) were compared to the heterozygote (+/-) and homozygote control (+/+) for growth characteristics and the presence of p53 protein isoforms. There were considerable morphological differences between the null cells and homozygote, with the null cells having irregular shapes and sizes, and densely staining pleomorphic nuclei. Growth curves showed the null cells to have essentially remained in log phase growth during the course of these studies, losing contact inhibition. Losses of all protein isoforms indicate a single locus origination, and suggest that the multiple protein isoforms observed are due to different net charges on the protein as a result of post-translational modification. These results confirm deactivation of the p53 gene by site-specific disruption of exon 5 as described by Donehower (Donehower et al., 1992).