Reference SummaryStorer RD, Toxicol Pathol 2001;29 Suppl():30-50

Title

 P53+/- hemizygous knockout mouse: overview of available data.

Authors

 Storer RD; French JE; Haseman J; Hajian G; LeGrand EK; Long GG; Mixson LA; Ochoa R; Sagartz JE; Soper KA

Journal

 Toxicol Pathol

Volume

 29 Suppl

Issue

Year

 2001

Pages

 30-50

Abstract

 The performance of the p53-/- transgenic (knockout) mouse model was evaluated through review of the data from 31 short-term carcinogenicity studies with 21 compounds tested as part of the International Life Sciences Institute's (ILSI) Alternatives to Carcinogenicity Testing (ACT) project, together with data from other studies which used comparable protocols. As expected based on the hypothesis for the model, a significant number (12/16 or 75%) of the genotoxic human and/or rodent carcinogens tested were positive and the positive control, p-cresidine, gave reproducible responses across laboratories (18/19 studies positive in bladder). An immunosuppressive human carcinogen, cyclosporin A, was positive for lymphomas but produced a similar response in wild type mice. Two hormones that are human tumorigens, diethylstilbestrol and 17beta-estradiol, gave positive and equivocal results, respectively, in the pituitary with p53-deficient mice showing a greater incidence of proliferative lesions than wild type. None of the 22 nongenotoxic rodent carcinogens that have been tested produced a positive response but 2 compounds in this category, chloroform and diethylhexylphthalate, were judged equivocal based on effects in liver and kidney respectively. Four genotoxic noncarcinogens and 6 nongenotoxic, noncarcinogens were also negative. In total (excluding compounds with equivocal results), 42 of 48 compounds or 88% gave results that were concordant with expectations. The technical lessons learned from the ILSI ACT-sponsored testing in the p53+/- model are discussed.

Links

 J:73019 – MGI References
11695560 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.129S7 "C57BL/6TacfBR-[KO] p53 N5 wild type mice were obtained from Taconic Farms, Inc., Germantown, NY, USA."
B6.129S7-Trp53tm1Brd/+ "C57BL/6TacfBR-[KO] p53 N5 heterozygous mice ... were obtained from Taconic Farms, Inc., Germantown, NY, USA."

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6.129S7-Trp53tm1Brd/+ Adrenal gland - Cortex adenoma Adrenal gland - Cortex

0 - 0.2
B6.129S7-Trp53tm1Brd/+ Adrenal gland - Cortex adenoma
  • phenacetin
 Adrenal gland - Cortex

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Adrenal gland - Medulla pheochromocytoma Adrenal gland - Medulla

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Adrenal gland - Medulla pheochromocytoma
  • Cyclosporin A
 Adrenal gland - Medulla

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

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Bone osteosarcoma
  • benzene
 Bone

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Bone osteosarcoma
  • Cyclosporin A
 Bone

0 - 6.7
B6.129S7-Trp53tm1Brd/+ CNS - Brain - Astrocyte astrocytoma CNS - Brain - Astrocyte

0
B6.129S7-Trp53tm1Brd/+ CNS - Brain - Astrocyte astrocytoma
  • Cyclosporin A
 CNS - Brain - Astrocyte

0 - 6.7
B6.129S7-Trp53tm1Brd/+ CNS - Meninges meningioma CNS - Meninges

0
B6.129S7-Trp53tm1Brd/+ CNS - Meninges meningioma
  • phenacetin
 CNS - Meninges

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Connective tissue - Fibroblast fibrosarcoma CNS - Meninges

0
B6.129S7-Trp53tm1Brd/+ Connective tissue - Fibroblast fibrosarcoma
  • cyclophosphamide (Cytoxan)
 CNS - Meninges

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Connective tissue - Fibroblast fibrosarcoma Subcutis

0 - 13.3
B6.129S7-Trp53tm1Brd/+ Connective tissue - Fibroblast fibrosarcoma
  • Cyclosporin A
 Subcutis

0 - 13.3
B6.129S7-Trp53tm1Brd/+ Connective tissue - Fibroblast fibrosarcoma
  • chloroform
 Subcutis

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Forestomach hyperplasia
  • ampicillin
 Forestomach

observed
B6.129S7-Trp53tm1Brd/+ Kidney transitional cell hyperplasia Kidney

0
B6.129S7-Trp53tm1Brd/+ Kidney transitional cell hyperplasia
  • diethylhexylphthalate (DEHP)
 Kidney

0 - 20
B6.129S7 Kidney transitional cell hyperplasia Kidney

0
B6.129S7 Kidney transitional cell hyperplasia
  • diethylhexylphthalate (DEHP)
 Kidney

0
B6.129S7-Trp53tm1Brd/+ Kidney transitional cell papilloma Kidney

0
B6.129S7-Trp53tm1Brd/+ Kidney transitional cell papilloma
  • diethylhexylphthalate (DEHP)
 Kidney

0 - 6.7
B6.129S7 Kidney transitional cell papilloma Kidney

0
B6.129S7 Kidney transitional cell papilloma
  • diethylhexylphthalate (DEHP)
 Kidney

0
B6.129S7-Trp53tm1Brd/+ Leukocyte - Lymphocyte hyperplasia Thymus

0
B6.129S7-Trp53tm1Brd/+ Leukocyte - Lymphocyte hyperplasia
  • benzene
 Thymus

13.3 - 20
B6.129S7-Trp53tm1Brd/+ Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Thymus

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma
  • cyclophosphamide (Cytoxan)
 Thymus

0
B6.129S7-Trp53tm1Brd/+ Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic Leukocyte - Myelocyte (Granulocyte)

0 - 0.2
B6.129S7-Trp53tm1Brd/+ Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic
  • cyclophosphamide (Cytoxan)
 Leukocyte - Myelocyte (Granulocyte)

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Leukocyte leukemia Leukocyte

1.7 - 2.9
B6.129S7-Trp53tm1Brd/+ Leukocyte lymphoma Leukocyte

0 - 20
B6.129S7-Trp53tm1Brd/+ Leukocyte lymphoma
  • benzene
 Leukocyte

6.7 - 20
B6.129S7-Trp53tm1Brd/+ Leukocyte lymphoma Thymus

0 - 13.3
B6.129S7-Trp53tm1Brd/+ Leukocyte lymphoma
  • benzene
 Thymus

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Leukocyte lymphoma
  • cyclophosphamide (Cytoxan)
 Leukocyte

0 - 53.3
B6.129S7-Trp53tm1Brd/+ Leukocyte lymphoma
  • phenacetin
 Thymus

0
B6.129S7-Trp53tm1Brd/+ Leukocyte lymphoma
  • Cyclosporin A
 Leukocyte

0 - 53.3
B6.129S7-Trp53tm1Brd/+ Leukocyte lymphoma
  • metaproterenol
 Leukocyte

0 - 6.7
B6.129S7 Leukocyte lymphoma Leukocyte

0 - 6.7
B6.129S7 Leukocyte lymphoma
  • cyclophosphamide (Cytoxan)
 Leukocyte

0 - 20
B6.129S7 Leukocyte lymphoma
  • Cyclosporin A
 Leukocyte

0 - 60
B6.129S7-Trp53tm1Brd/+ Liver adenoma Liver

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Liver adenoma
  • chloroform
 Liver

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Liver carcinoma Liver

0
B6.129S7-Trp53tm1Brd/+ Liver carcinoma
  • chloroform
 Liver

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Liver tumor Liver

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Liver tumor
  • chloroform
 Liver

0 - 13.3
B6.129S7 Liver tumor Liver

0
B6.129S7 Liver tumor
  • chloroform
 Liver

0
B6.129S7-Trp53tm1Brd/+ Lung adenoma Lung

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Lung adenoma
  • Cyclosporin A
 Lung

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Lung adenoma
  • chloroform
 Lung

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Lung hyperplasia Lung

0
B6.129S7-Trp53tm1Brd/+ Lung hyperplasia
  • chloroform
 Lung

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Mesodermal cell/mesoblast sarcoma Subcutis

0 - 13.3
B6.129S7-Trp53tm1Brd/+ Mesodermal cell/mesoblast sarcoma CNS - Meninges

0 - 0.2
B6.129S7-Trp53tm1Brd/+ Mesodermal cell/mesoblast sarcoma Prostate gland

0.2
B6.129S7-Trp53tm1Brd/+ Mesodermal cell/mesoblast sarcoma Urinary bladder

0
B6.129S7-Trp53tm1Brd/+ Mesodermal cell/mesoblast sarcoma
  • p-cresidine
 Urinary bladder

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Mesodermal cell/mesoblast sarcoma
  • benzene
 Subcutis

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Mesodermal cell/mesoblast sarcoma
  • cyclophosphamide (Cytoxan)
 Subcutis

0 - 13.3
B6.129S7-Trp53tm1Brd/+ Mesodermal cell/mesoblast sarcoma
  • phenacetin
 Subcutis

6.7 - 26.7
B6.129S7-Trp53tm1Brd/+ Muscle - Smooth leiomyosarcoma Prostate gland

0.2
B6.129S7-Trp53tm1Brd/+ Muscle - Striated - Skeletal rhabdomyosarcoma Lung

0 - 0.2
B6.129S7-Trp53tm1Brd/+ Muscle - Striated - Skeletal rhabdomyosarcoma Muscle - Striated - Skeletal

0
B6.129S7-Trp53tm1Brd/+ Muscle - Striated - Skeletal rhabdomyosarcoma
  • metaproterenol
 Muscle - Striated - Skeletal

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Neuroblast neuroblastoma - olfactory Nose - Nasal cavity

0 - 0.2
B6.129S7-Trp53tm1Brd/+ Neuroblast neuroblastoma - olfactory
  • Cyclosporin A
 Nose - Nasal cavity

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Oral cavity squamous cell carcinoma Oral cavity

0
B6.129S7-Trp53tm1Brd/+ Oral cavity squamous cell carcinoma
  • benzene
 Oral cavity

0 - 6.7
B6.129S7-Trp53tm1Brd/+ Pancreas carcinoma Pancreas

0 - 0.2
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars distalis adenoma Pituitary gland - Pars distalis

0
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars distalis adenoma
  • diethylstilbestrol (DES)
 Pituitary gland - Pars distalis

13.3
B6.129S7 Pituitary gland - Pars distalis adenoma Pituitary gland - Pars distalis

0
B6.129S7 Pituitary gland - Pars distalis adenoma
  • diethylstilbestrol (DES)
 Pituitary gland - Pars distalis

0
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars distalis hyperplasia Pituitary gland - Pars distalis

0
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars distalis hyperplasia
  • 17beta-estradiol (E2)
 Pituitary gland - Pars distalis

0 - 80
B6.129S7 Pituitary gland - Pars distalis hyperplasia Pituitary gland - Pars distalis

0
B6.129S7 Pituitary gland - Pars distalis hyperplasia
  • 17beta-estradiol (E2)
 Pituitary gland - Pars distalis

33.3
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars distalis hyperplasia - diffuse Pituitary gland - Pars distalis

0
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars distalis hyperplasia - diffuse
  • diethylstilbestrol (DES)
 Pituitary gland - Pars distalis

93.3 - 100
B6.129S7 Pituitary gland - Pars distalis hyperplasia - diffuse Pituitary gland - Pars distalis

0
B6.129S7 Pituitary gland - Pars distalis hyperplasia - diffuse
  • diethylstilbestrol (DES)
 Pituitary gland - Pars distalis

100
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars distalis hyperplasia - nodular Pituitary gland - Pars distalis

0
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars distalis hyperplasia - nodular
  • diethylstilbestrol (DES)
 Pituitary gland - Pars distalis

33.3 - 53.3
B6.129S7 Pituitary gland - Pars distalis hyperplasia - nodular Pituitary gland - Pars distalis

0
B6.129S7 Pituitary gland - Pars distalis hyperplasia - nodular
  • diethylstilbestrol (DES)
 Pituitary gland - Pars distalis

6.7 - 14.3
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars intermedia adenoma Pituitary gland - Pars intermedia

0
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars intermedia adenoma
  • diethylstilbestrol (DES)
 Pituitary gland - Pars intermedia

6.7
B6.129S7 Pituitary gland - Pars intermedia adenoma Pituitary gland - Pars intermedia

0
B6.129S7 Pituitary gland - Pars intermedia adenoma
  • diethylstilbestrol (DES)
 Pituitary gland - Pars intermedia

0
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars intermedia hyperplasia - diffuse Pituitary gland - Pars intermedia

0
B6.129S7-Trp53tm1Brd/+ Pituitary gland - Pars intermedia hyperplasia - diffuse
  • diethylstilbestrol (DES)
 Pituitary gland - Pars intermedia

93.3 - 100
B6.129S7 Pituitary gland - Pars intermedia hyperplasia - diffuse Pituitary gland - Pars intermedia

0
B6.129S7 Pituitary gland - Pars intermedia hyperplasia - diffuse
  • diethylstilbestrol (DES)
 Pituitary gland - Pars intermedia

100
B6.129S7-Trp53tm1Brd/+ Pituitary gland adenoma Pituitary gland

0
B6.129S7-Trp53tm1Brd/+ Pituitary gland adenoma
  • 17beta-estradiol (E2)
 Pituitary gland

0 - 6.7
B6.129S7 Pituitary gland adenoma Pituitary gland

0
B6.129S7 Pituitary gland adenoma
  • 17beta-estradiol (E2)
 Pituitary gland

0
B6.129S7-Trp53tm1Brd/+ Pituitary gland hyperplasia - focal Pituitary gland

0
B6.129S7-Trp53tm1Brd/+ Pituitary gland hyperplasia - focal
  • 17beta-estradiol (E2)
 Pituitary gland

0 - 6.7
B6.129S7 Pituitary gland hyperplasia - focal Pituitary gland

0
B6.129S7 Pituitary gland hyperplasia - focal
  • 17beta-estradiol (E2)
 Pituitary gland

0
B6.129S7-Trp53tm1Brd/+ Stomach - Glandular hyperplasia
  • ampicillin
 Stomach - Glandular

observed
B6.129S7-Trp53tm1Brd/+ Testis - Leydig cell (Interstitial cell) hyperplasia Testis - Leydig cell (Interstitial cell)

0
B6.129S7-Trp53tm1Brd/+ Testis - Leydig cell (Interstitial cell) hyperplasia
  • diethylstilbestrol (DES)
 Testis - Leydig cell (Interstitial cell)

26.7
B6.129S7 Testis - Leydig cell (Interstitial cell) hyperplasia Testis - Leydig cell (Interstitial cell)

0
B6.129S7 Testis - Leydig cell (Interstitial cell) hyperplasia
  • diethylstilbestrol (DES)
 Testis - Leydig cell (Interstitial cell)

15.4 - 20
B6.129S7-Trp53tm1Brd/+ Testis - Leydig cell (Interstitial cell) tumor Testis - Leydig cell (Interstitial cell)

0
B6.129S7-Trp53tm1Brd/+ Testis - Leydig cell (Interstitial cell) tumor
  • diethylstilbestrol (DES)
 Testis - Leydig cell (Interstitial cell)

0 - 13.3
B6.129S7 Testis - Leydig cell (Interstitial cell) tumor Testis - Leydig cell (Interstitial cell)

0
B6.129S7 Testis - Leydig cell (Interstitial cell) tumor
  • diethylstilbestrol (DES)
 Testis - Leydig cell (Interstitial cell)

0
B6.129S7-Trp53tm1Brd/+ Thymus hyperplasia - atypical Thymus

0
B6.129S7-Trp53tm1Brd/+ Thymus hyperplasia - atypical
  • benzene
 Thymus

0 - 26.7
B6.129S7-Trp53tm1Brd/+ Thyroid gland - Follicular cell hyperplasia
  • sulfamethoxazole (SMX)
 Thyroid gland - Follicular cell

observed
B6.129S7-Trp53tm1Brd/+ Ureter hyperplasia Ureter

0
B6.129S7-Trp53tm1Brd/+ Ureter hyperplasia
  • diethylhexylphthalate (DEHP)
 Ureter

0 - 6.7
B6.129S7 Ureter hyperplasia Ureter

0
B6.129S7 Ureter hyperplasia
  • diethylhexylphthalate (DEHP)
 Ureter

0
B6.129S7-Trp53tm1Brd/+ Urinary bladder atypia Urinary bladder

0
B6.129S7-Trp53tm1Brd/+ Urinary bladder atypia
  • p-cresidine
 Urinary bladder

33.3 - 40
B6.129S7-Trp53tm1Brd/+ Urinary bladder dysplasia Urinary bladder

0
B6.129S7-Trp53tm1Brd/+ Urinary bladder dysplasia
  • p-cresidine
 Urinary bladder

0 - 46.7
B6.129S7-Trp53tm1Brd/+ Urinary bladder hyperplasia Urinary bladder

0
B6.129S7-Trp53tm1Brd/+ Urinary bladder hyperplasia
  • p-cresidine
 Urinary bladder

73.3 - 100
B6.129S7-Trp53tm1Brd/+ Urinary bladder metaplasia - squamous Urinary bladder

0
B6.129S7-Trp53tm1Brd/+ Urinary bladder metaplasia - squamous
  • p-cresidine
 Urinary bladder

26.7 - 53.3
B6.129S7-Trp53tm1Brd/+ Urinary bladder neoplasm Urinary bladder

0
B6.129S7-Trp53tm1Brd/+ Urinary bladder neoplasm
  • p-cresidine
 Urinary bladder

0
B6.129S7-Trp53tm1Brd/+ Urinary bladder papilloma Urinary bladder

0
B6.129S7-Trp53tm1Brd/+ Urinary bladder papilloma
  • p-cresidine
 Urinary bladder

13.3 - 26.7
B6.129S7-Trp53tm1Brd/+ Urinary bladder squamous cell carcinoma Urinary bladder

0
B6.129S7-Trp53tm1Brd/+ Urinary bladder squamous cell carcinoma
  • p-cresidine
 Urinary bladder

13.3 - 33.3
B6.129S7-Trp53tm1Brd/+ Urinary bladder transitional cell carcinoma Urinary bladder

0
B6.129S7-Trp53tm1Brd/+ Urinary bladder transitional cell carcinoma
  • p-cresidine
 Urinary bladder

6.7 - 73.3
B6.129S7 Urinary bladder transitional cell carcinoma Urinary bladder

0
B6.129S7 Urinary bladder transitional cell carcinoma
  • p-cresidine
 Urinary bladder

6.7
B6.129S7-Trp53tm1Brd/+ Urinary bladder tumor
  • p-cresidine
 Urinary bladder

60 - 86.7
B6.129S7-Trp53tm1Brd/+ Uterus - Endometrium - Stroma polyp Uterus - Endometrium - Stroma

0
B6.129S7-Trp53tm1Brd/+ Uterus - Endometrium - Stroma polyp
  • cyclophosphamide (Cytoxan)
 Uterus - Endometrium - Stroma

0 - 6.7
B6.129S7-Trp53tm1Brd/+ (Unspecified organ) tumor (Unspecified organ)

2.8 - 11.3