Reference SummaryLavigueur A, Mol Cell Biol 1989 Sep;9(9):3982-91

Title

 High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene.

Authors

 Lavigueur A; Maltby V; Mock D; Rossant J; Pawson T; Bernstein A

Journal

 Mol Cell Biol

Volume

 9

Issue

 9

Year

 1989

Pages

 3982-91

Abstract

 We have investigated the role of the p53 gene in oncogenesis in vivo by generating transgenic mice carrying murine p53 genomic fragments isolated from a mouse Friend erythroleukemia cell line or BALB/c mouse liver DNA. Elevated levels of p53 mRNA were detected in several tissues of two transgenic lines tested. Increased levels of p53 protein were also detected in most of the tissues analyzed by Western blotting (immunoblotting). Because both transgenes encoded p53 proteins that were antigenically distinct from wild-type p53, it was possible to demonstrate that overexpression of the p53 protein was mostly, if not entirely, due to the expression of the transgenes. Neoplasms developed in 20% of the transgenic mice, with a high incidence of lung adenocarcinomas, osteo-sarcomas, and lymphomas. Tissues such as ovaries that expressed the transgene at high levels were not at higher risk of malignant transformation than tissues expressing p53 protein at much lower levels. The long latent period and low penetrance suggest that overexpression of p53 alone is not sufficient to induce malignancies and that additional events are required. These observations provide direct evidence that mutant alleles of the p53 oncogene have oncogenic potential in vivo and that different cell types show intrinsic differences in susceptibility to malignant transformation by p53. Since recent data suggest that p53 may be a recessive oncogene, it is possible that the elevated tumor incidence results from functional inactivation of endogenous p53 by overexpression of the mutant transgene. The high incidence of lung and bone tumors suggests that p53 transgenic mice may provide a useful model to investigate the molecular events that underlie these malignancies in humans.

Links

 J:19870 – MGI References
2476668 – National Library of Medicine/PubMed

Strain Notes

Strain Note
CD-1 Expression of the wild type allele of the Trp53 gene was reported to not be detected in the liver, spleen, and thymus of these mice.
The wild type allele of the Trp53 gene was reported to be slightly expressed in the spleen, lungs, liver, kidneys of these mice.
CD-1-Tg(Trp53A135V)L2Ber The "pL53" transgene was reported to be highly expressed in the spleen, thymus, and lymph nodes, and expressed in the ovaries of these mice. Little or no expression was reported to have been observed in the liver and lungs of these mice.
CD-1-Tg(Trp53A135V)L3Ber The "pL53" transgene was reported to be highly expressed in the spleen, thymus, and lymph nodes, and expressed in the lungs, liver, and kidneys of these mice.
CD-1-Tg(Trp53R193P)2Ber Expression of the "p53" transgene was reported to not be detected in the heart and blood of these mice.
The "p53" transgene was reported to be highly expressed in the spleen, thymus, lymph nodes, and ovaries, expressed in the lungs, liver, kidney, testis, and brain, and slightly expressed in the skeletal muscle of these mice.
CD-1-Tg(Trp53R193P)3Ber The "p53" transgene was reported to be expressed in the spleen of these mice.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
CD-1-Tg(Trp53R193P)1Ber Bone osteosarcoma Bone

observed
CD-1-Tg(Trp53R193P)2Ber Bone osteosarcoma Bone

observed
CD-1-Tg(Trp53R193P)3Ber Bone osteosarcoma Bone

observed
CD-1-Tg(Trp53A135V)L2Ber Bone osteosarcoma Bone

observed
CD-1-Tg(Trp53A135V)L3Ber Bone osteosarcoma Bone

observed
CD-1 Bone osteosarcoma Bone

0.6
CD-1-Tg(Trp53R193P)2Ber Connective tissue - Fibroblast fibrosarcoma Connective tissue - Fibroblast

observed
CD-1-Tg(Trp53R193P)1Ber Leukocyte lymphoma Leukocyte

observed
CD-1-Tg(Trp53R193P)2Ber Leukocyte lymphoma Leukocyte

observed
CD-1-Tg(Trp53A135V)L1Ber Leukocyte lymphoma Leukocyte

observed
CD-1-Tg(Trp53A135V)L2Ber Leukocyte lymphoma Leukocyte

observed
CD-1-Tg(Trp53A135V)L3Ber Leukocyte lymphoma Leukocyte

observed
CD-1 Leukocyte lymphoma Leukocyte

1.5
CD-1-Tg(Trp53R193P)1Ber Lung adenocarcinoma Lung

observed
CD-1-Tg(Trp53R193P)2Ber Lung adenocarcinoma Lung

observed
CD-1 Lung adenocarcinoma Lung

1.0
CD-1-Tg(Trp53R193P)1Ber Muscle - Striated - Skeletal rhabdomyosarcoma Muscle - Striated - Skeletal

observed
CD-1-Tg(Trp53R193P)2Ber Muscle - Striated - Skeletal rhabdomyosarcoma Muscle - Striated - Skeletal

observed
CD-1-Tg(Trp53R193P)2Ber Neuroblast neuroblastoma Adrenal gland

observed
CD-1-Tg(Trp53R193P)1Ber Ovary tumor Ovary

0
CD-1-Tg(Trp53R193P)2Ber Ovary tumor Ovary

0
CD-1-Tg(Trp53R193P)3Ber Ovary tumor Ovary

0
CD-1-Tg(Trp53A135V)L1Ber Ovary tumor Ovary

0
CD-1-Tg(Trp53A135V)L2Ber Ovary tumor Ovary

0
CD-1-Tg(Trp53A135V)L3Ber Ovary tumor Ovary

0
CD-1-Tg(Trp53R193P)1Ber Skin carcinoma Skin

observed
CD-1-Tg(Trp53R193P)2Ber Skin carcinoma Skin

observed
CD-1-Tg(Trp53R193P)1Ber Testis carcinoma Testis

observed
CD-1 Thymus thymoma Thymus

1.6