Reference SummaryNister M, Oncogene 2005 May 19;24(22):3563-73

Title

 p53 must be competent for transcriptional regulation to suppress tumor formation.

Authors

 Nister M; Tang M; Zhang XQ; Yin C; Beeche M; Hu X; Enblad G; van Dyke T; Wahl GM

Journal

 Oncogene

Volume

 24

Issue

 22

Year

 2005

Pages

 3563-73

Abstract

 In vitro studies suggest that effective tumor suppression by p53 requires multiple domains to execute transcription-dependent and transcription-independent functions. We generated a mutant p53 allele in mice, p53(W25QL26S) (p53(QS)), containing an inactive transactivation domain to evaluate the importance of transactivation for p53-mediated tumor suppression. Recently, we discovered that the allele also contains a valine substitution for alanine at codon 135, which borders the DNA-binding domain. We found that p53(QSval135) bound to chromatin albeit less well than p53(QSala135), but both were equally deficient in transcriptional regulation, apoptosis induction in mouse embryo fibroblasts (MEFs), and suppression of tumor formation by E1A, Ha-Ras transformed MEFs. p53(QSval135) mice and p53-null mice exhibited identical tumor development kinetics and spectra in spontaneous and oncogene-initiated tumorigenicity assays, when tested in a homo- and heterozygous configuration. The p53(QSval135) allele did not have dominant negative functions and behaved as a null allele. Taken together, these data indicate that effective tumor suppression requires the transcriptional regulation function of p53, and they suggest that transactivation independent functions of p53 are unlikely to contribute significantly to tumor suppression in vivo.

Links

 J:153341 – MGI References
15750633 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6;129 The mutation carried by littermates was generated using ES cells with a 129S4/SvJae genetic background. The paper stated that the mice had been "bred to >=75% C57BL/6 background". No information was given regarding any other strains that might have been involved.
B6;129-Trp53tm1Wahl The mutation was generated using ES cells with a 129S4/SvJae genetic background. The paper stated that the mice had been "bred to >=75% C57BL/6 background". No information was given regarding any other strains that might have been involved.
B6;129-Trp53tm1Wahl/+ The mutation was generated using ES cells with a 129S4/SvJae genetic background. The paper stated that the mice had been "bred to >=75% C57BL/6 background". No information was given regarding any other strains that might have been involved.
B6.129S7 The mutation carried by littermates was generated using ES cells with a 129S7/SvEvBrd-Hprt+ genetic background. The paper stated that the mice had a "close to 100% C57BL/6" background.
B6.129S7-Trp53tm1Brd The mutation was generated using ES cells with a 129S7/SvEvBrd-Hprt+ genetic background. The paper stated that the mice had a "close to 100% C57BL/6" background.
B6.129S7-Trp53tm1Brd/+ The mutation was generated using ES cells with a 129S7/SvEvBrd-Hprt+ genetic background. The paper stated that the mice had a "close to 100% C57BL/6" background.
STOCK Tg(LPV-TAg121)2Tvd Transgenic mice on a mixed C57BL/6 and DBA/2 background were crossed to targeted mutant mice on a "close to 100% C57BL/6" background. The KO was generated in a 129S7/SvEvBrd-Hprt+ background.
STOCK Tg(LPV-TAg121)2Tvd Transgenic mice on a mixed C57BL/6 and DBA/2 background were crossed to targeted mutant mice on a predominantly C57BL/6 background (>=75%). The KO was generated in a 129S4/SvJae background.
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Brd Transgenic mice on a mixed C57BL/6 and DBA/2 background were crossed to targeted mutant mice on a "close to 100% C57BL/6" background. The KO was generated in a 129S7/SvEvBrd-Hprt+ background.
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Brd/+ Transgenic mice on a mixed C57BL/6 and DBA/2 background were crossed to targeted mutant mice on a "close to 100% C57BL/6" background. The KO was generated in a 129S7/SvEvBrd-Hprt+ background.
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Wahl Transgenic mice on a mixed C57BL/6 and DBA/2 background were crossed to targeted mutant mice on a predominantly C57BL/6 background (>=75%). The KO was generated in a 129S4/SvJae background.
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Wahl/+ Transgenic mice on a mixed C57BL/6 and DBA/2 background were crossed to targeted mutant mice on a predominantly C57BL/6 background (>=75%). The KO was generated in a 129S4/SvJae background.
Visual Summary Grid

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6;129-Trp53tm1Wahl/+ Abdominal wall tumor - anaplastic Abdominal wall

0.5
B6;129-Trp53tm1Wahl/+ Adipose tissue liposarcoma Adipose tissue

observed
B6;129-Trp53tm1Wahl Bone osteosarcoma Bone

0
B6;129-Trp53tm1Wahl/+ Bone osteosarcoma Bone

7.5
B6.129S7-Trp53tm1Brd Bone osteosarcoma Bone

0
B6.129S7-Trp53tm1Brd/+ Bone osteosarcoma Bone

8.8
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Wahl CNS - Brain - Choroid plexus dysplasia CNS - Brain - Choroid plexus

observed
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Wahl/+ CNS - Brain - Choroid plexus dysplasia CNS - Brain - Choroid plexus

observed
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Brd CNS - Brain - Choroid plexus dysplasia CNS - Brain - Choroid plexus

observed
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Brd/+ CNS - Brain - Choroid plexus dysplasia CNS - Brain - Choroid plexus

observed
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Wahl CNS - Brain - Choroid plexus tumor CNS - Brain - Choroid plexus

100
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Wahl/+ CNS - Brain - Choroid plexus tumor CNS - Brain - Choroid plexus

100
STOCK Tg(LPV-TAg121)2Tvd CNS - Brain - Choroid plexus tumor CNS - Brain - Choroid plexus

100
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Brd CNS - Brain - Choroid plexus tumor CNS - Brain - Choroid plexus

100
STOCK Tg(LPV-TAg121)2Tvd Trp53tm1Brd/+ CNS - Brain - Choroid plexus tumor CNS - Brain - Choroid plexus

100
STOCK Tg(LPV-TAg121)2Tvd CNS - Brain - Choroid plexus tumor CNS - Brain - Choroid plexus

100
B6;129-Trp53tm1Wahl CNS - Brain glioma - malignant CNS - Brain

1.3
B6;129-Trp53tm1Wahl/+ CNS - Brain glioma - malignant CNS - Brain

0.5
B6;129-Trp53tm1Wahl CNS - Spinal cord glioma - malignant CNS - Spinal cord

1.3
B6;129-Trp53tm1Wahl Cheek tumor - anaplastic Cheek

1.3
B6;129-Trp53tm1Wahl Connective tissue - Fibroblast fibrosarcoma Connective tissue - Fibroblast

5.3
B6;129-Trp53tm1Wahl/+ Connective tissue - Fibroblast fibrosarcoma Connective tissue - Fibroblast

3.5
B6.129S7-Trp53tm1Brd Connective tissue - Fibroblast fibrosarcoma Connective tissue - Fibroblast

3.2
B6.129S7-Trp53tm1Brd/+ Connective tissue - Fibroblast fibrosarcoma Connective tissue - Fibroblast

6.1
B6.129S7-Trp53tm1Brd/+ Germ cell (sex not specified) teratocarcinoma Germ cell (sex not specified)

0.7
B6;129-Trp53tm1Wahl Gonad (sex not specified) tumor Gonad (sex not specified)

1.3
B6;129-Trp53tm1Wahl Leukocyte lymphoma Leukocyte

25 - 62
B6;129-Trp53tm1Wahl Leukocyte lymphoma Thymus

37
B6;129-Trp53tm1Wahl/+ Leukocyte lymphoma Leukocyte

9.0 - 12
B6;129-Trp53tm1Wahl/+ Leukocyte lymphoma Thymus

3.5
B6.129S7-Trp53tm1Brd Leukocyte lymphoma Leukocyte

35 - 68
B6.129S7-Trp53tm1Brd Leukocyte lymphoma Thymus

32
B6.129S7-Trp53tm1Brd/+ Leukocyte lymphoma Leukocyte

8.2 - 10
B6.129S7-Trp53tm1Brd/+ Leukocyte lymphoma Thymus

2.0
B6;129-Trp53tm1Wahl/+ Liver adenocarcinoma Liver

0.5
B6;129-Trp53tm1Wahl/+ Liver carcinoma Liver

0.5
B6.129S7-Trp53tm1Brd/+ Liver carcinoma Liver

0.7
B6;129-Trp53tm1Wahl/+ Lung carcinoma Lung

0.5
B6;129-Trp53tm1Wahl Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

20
B6;129-Trp53tm1Wahl/+ Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

15
B6.129S7-Trp53tm1Brd Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

16
B6.129S7-Trp53tm1Brd/+ Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

16
B6;129-Trp53tm1Wahl Mesodermal cell/mesoblast sarcoma - poorly differentiated Mesodermal cell/mesoblast

observed
B6.129S7-Trp53tm1Brd Mesodermal cell/mesoblast sarcoma - poorly differentiated Mesodermal cell/mesoblast

observed
B6;129-Trp53tm1Wahl Mesodermal cell/mesoblast sarcoma - well differentiated Mesodermal cell/mesoblast

observed
B6.129S7-Trp53tm1Brd Mesodermal cell/mesoblast sarcoma - well differentiated Mesodermal cell/mesoblast

observed
B6.129S7-Trp53tm1Brd/+ Salivary gland carcinoma Salivary gland

0.7
B6;129-Trp53tm1Wahl/+ Skin carcinoma Skin

1.0
B6.129S7-Trp53tm1Brd/+ Skin carcinoma Skin

0.7
B6.129S7-Trp53tm1Brd/+ Skin papilloma Skin

0.7
B6;129-Trp53tm1Wahl/+ Skin squamous cell carcinoma Skin

1.5
B6;129-Trp53tm1Wahl/+ Skin squamous cell papilloma Skin

0.5
B6;129-Trp53tm1Wahl/+ Testis - Germ cell teratoma Testis - Germ cell

0.5
B6.129S7-Trp53tm1Brd/+ Testis tumor - cystic Testis

0.7
B6;129-Trp53tm1Wahl Testis tumor - malignant Testis

1.3
B6.129S7-Trp53tm1Brd/+ (Unspecified organ) adenocarcinoma (Unspecified organ)

0.7
B6;129-Trp53tm1Wahl (Unspecified organ) angiosarcoma (Unspecified organ)

9.2
B6;129-Trp53tm1Wahl/+ (Unspecified organ) angiosarcoma (Unspecified organ)

1.5
B6.129S7-Trp53tm1Brd (Unspecified organ) angiosarcoma (Unspecified organ)

3.2
B6.129S7-Trp53tm1Brd/+ (Unspecified organ) angiosarcoma (Unspecified organ)

0.7
B6;129-Trp53tm1Wahl (Unspecified organ) carcinoma (Unspecified organ)

0
B6;129-Trp53tm1Wahl (Unspecified organ) histiocytoma - fibrous - malignant (Unspecified organ)

observed
B6.129S7-Trp53tm1Brd (Unspecified organ) histiocytoma - fibrous - malignant (Unspecified organ)

observed
B6;129-Trp53tm1Wahl (Unspecified organ) tumor (Unspecified organ)

88 - 100
B6;129-Trp53tm1Wahl/+ (Unspecified organ) tumor (Unspecified organ)

34 - 90
B6;129 (Unspecified organ) tumor (Unspecified organ)

26
B6.129S7-Trp53tm1Brd (Unspecified organ) tumor (Unspecified organ)

84 - 100
B6.129S7-Trp53tm1Brd/+ (Unspecified organ) tumor (Unspecified organ)

31 - 72
B6.129S7 (Unspecified organ) tumor (Unspecified organ)

26
B6;129-Trp53tm1Wahl/+ (Unspecified organ) tumor - anaplastic (Unspecified organ)

0.5