| First Author | Liu G | Year | 2000 |
| Journal | Proc Natl Acad Sci U S A | Volume | 97 |
| Issue | 8 | Pages | 4174-9 |
| PubMed ID | 10760284 | Mgi Jnum | J:61683 |
| Mgi Id | MGI:1355421 | Doi | 10.1073/pnas.97.8.4174 |
| Citation | Liu G, et al. (2000) High metastatic potential in mice inheriting a targeted p53 missense mutation. Proc Natl Acad Sci U S A 97(8):4174-9 |
| abstractText | To understand the relevance of p53 missense mutations in vivo, we generated a mouse containing an arg-to-his substitution at p53 amino acid 172, which corresponds to the R175H hot-spot mutation in human tumors by homologous recombination. Inadvertently, this mouse contains the additional deletion of a G nucleotide at a splice junction that attenuates levels of mutant p53 to near wild-type levels. Mice heterozygous for the mutant allele differed from p53(+/-) mice in tumor spectrum, with a significant increase in the number of carcinomas and a slight decrease in the number of lymphomas. More importantly, the osteosarcomas and carcinomas that developed in these mutant mice frequently metastasized (69% and 40%, respectively). In contrast, metastasis is rare in osteosarcomas of p53(+/-) mice. Loss of heterozygosity studies of tumors indicated loss of heterozygosity in only 1 of 11 tumors. These data indicate clear differences between a p53 missense mutation and a null allele in tumorigenesis in vivo and suggest that the p53R172HDeltag mutant represents a gain-of-function allele. |
