Reference SummaryGarcia-Cao I, EMBO J 2002 Nov 15;21(22):6225-35

Title

'Super p53' mice exhibit enhanced DNA damage response, are tumor resistant and age normally.

Authors

Garcia-Cao I; Garcia-Cao M; Martin-Caballero J; Criado LM; Klatt P; Flores JM; Weill JC; Blasco MA; Serrano M

Journal

EMBO J

Volume

21

Issue

22

Year

2002

Pages

6225-35

Abstract

The tumor suppressor p53 is critical in preventing cancer due to its ability to trigger proliferation arrest and cell death upon the occurrence of a variety of stresses, most notably, DNA damage and oncogenic stress. Here, we report the generation and characterization of mice carrying supernumerary copies of the p53 gene in the form of large genomic transgenes. Prior to this, we demonstrate that the p53 transgenic allele (p53-tg), when present in a p53-null genetic background, behaves as a functional replica of the endogenous gene. 'Super p53' mice, carrying p53-tg alleles in addition to the two endogenous alleles, exhibit an enhanced response to DNA damage. Importantly, 'super p53' mice are significantly protected from cancer when compared with normal mice. Finally, in contrast to previously reported mice with constitutively active p53, 'super p53' mice do not show any indication of premature aging, probably reflecting the fact that p53 is under normal regulatory control. Together, our results prove that cancer resistance can be enhanced by a simple genetic modification and in the absence of undesirable effects.

Links

J:80311 – MGI References
12426394 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6;CBA The contribution of C57BL/6 to the genetic background of these mice was reported as 87.5% or higher.
B6;CBA-Tg(Trp53)1Srn The contribution of C57BL/6 to the genetic background of these mice was reported as 87.5% or higher.

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6;CBA-Tg(Trp53)1Srn CNS - Brain tumor CNS - Brain

0

B6;CBA-Tg(Trp53)1Srn Connective tissue - Fibroblast fibrosarcoma
  • 3-methylcholanthrene (MCA) (3-MC)
Connective tissue - Fibroblast

33

B6;CBA Connective tissue - Fibroblast fibrosarcoma
  • 3-methylcholanthrene (MCA) (3-MC)
Connective tissue - Fibroblast

92

B6;CBA-Tg(Trp53)1Srn Esophagus tumor Esophagus

0

B6;CBA-Tg(Trp53)1Srn Heart tumor Heart

0

B6;CBA-Tg(Trp53)1Srn Intestine - Large Intestine tumor Intestine - Large Intestine

0

B6;CBA-Tg(Trp53)1Srn Intestine - Small Intestine tumor Intestine - Small Intestine

0

B6;CBA-Tg(Trp53)1Srn Kidney tumor Kidney

0

B6;CBA-Tg(Trp53)1Srn Leukocyte lymphoma Leukocyte

17

B6;CBA Leukocyte lymphoma Leukocyte

19

B6;CBA-Tg(Trp53)1Srn Liver tumor Liver

0

B6;CBA Lung adenoma Lung

14

B6;CBA-Tg(Trp53)1Srn Lung tumor Lung

0

B6;CBA-Tg(Trp53)1Srn Ovary tumor Ovary

0

B6;CBA-Tg(Trp53)1Srn Pancreas tumor Pancreas

0

B6;CBA-Tg(Trp53)1Srn Pituitary gland tumor Pituitary gland

0

B6;CBA-Tg(Trp53)1Srn Prostate gland tumor Prostate gland

0

B6;CBA-Tg(Trp53)1Srn Salivary gland tumor Salivary gland

0

B6;CBA-Tg(Trp53)1Srn Skin tumor Skin

0

B6;CBA-Tg(Trp53)1Srn Spleen tumor Spleen

0

B6;CBA-Tg(Trp53)1Srn Stomach tumor Stomach

0

B6;CBA-Tg(Trp53)1Srn Testis tumor Testis

0

B6;CBA-Tg(Trp53)1Srn Thyroid gland tumor Thyroid gland

0

B6;CBA-Tg(Trp53)1Srn Urinary bladder transitional cell carcinoma
  • N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
Urinary bladder

67

B6;CBA Urinary bladder transitional cell carcinoma
  • N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
Urinary bladder

83

B6;CBA-Tg(Trp53)1Srn Urinary bladder tumor Urinary bladder

0

B6;CBA-Tg(Trp53)1Srn Uterus tumor Uterus

0

B6;CBA-Tg(Trp53)1Srn (Unspecified organ) tumor (Unspecified organ)

0 - 17

B6;CBA (Unspecified organ) tumor (Unspecified organ)

47