Retention of p53val135 wild-type function in transgenic mice.
We targeted a mutant p53 gene (val135), previously shown to cause tumors in transgenic mice, to the kidney and eye using a gamma-glutamyltranspeptidase promoter. Although transgene RNA was expressed in both tissues, and mutant protein could be detected at high levels in the kidney and was appropriately localized to the nuclei of proximal tubules, no gross or microscopic lesions developed, even when mice were held as long as 75 weeks. When these mice were crossed with transgenic mice carrying HrasT24 (containing a codon 12 mutation) driven by the same promoter, the p53val135 transgene partially suppressed the mutant ras phenotype (proximal tubular hyperplasia and adenomas and carcinomas of the ciliary body and retinal pigment epithelium). The kidneys of double transgenic mice younger than 25 weeks showed less tubular hyperplasia and cystic change than littermates carrying gamma-glutamyltranspeptidase(I)rasT24 alone. By 33 weeks, there was no difference in the severity of the kidney lesions. The eye lesions were less aggressive, and no malignant lesions were identified. Our findings are consistent with the work of others, indicating that p53val135 is not tumorigenic under all conditions; in fact, in some circumstances, it retains some of the suppressing activity of wild-type p53.
Schaffner
D L
DL
Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
Chévez-Barrios
P
P
Huang
S L
SL
Barrios
R
R
Dickey
B F
BF
Shaker
M R
MR
Rajagopalan
S
S
Habib
G M
GM
Lebovitz
R M
RM
Lieberman
M W
MW
D000409:Alanine / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D016158:Genes, p53; D011905:Genes, ras; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D012313:RNA / Q000032:analysis; D019076:Transgenes; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics; D014633:Valine / Q000235:genetics*; D005723:gamma-Glutamyltransferase / Q000235:genetics
D016159:Tumor Suppressor Protein p53; D012313:RNA; D005723:gamma-Glutamyltransferase; D014633:Valine; D000409:Alanine