Reference SummaryChan CS, Life Sci Alliance 2021 Mar;4(3):

Title

 Genetic and stochastic influences upon tumor formation and tumor types in Li-Fraumeni mouse models.

Authors

 Chan CS; Sun Y; Ke H; Zhao Y; Belete M; Zhang C; Feng Z; Levine AJ; Hu W

Journal

 Life Sci Alliance

Volume

 4

Issue

 3

Year

 2021

Pages

Abstract

 p53 is the most frequently mutated gene in human cancers. Li-Fraumeni syndrome patients inheriting heterozygous p53 mutations often have a much-increased risk to develop cancer(s) at early ages. Recent studies suggest that some individuals inherited p53 mutations do not have the early onset or high frequency of cancers. These observations suggest that other genetic, environmental, immunological, epigenetic, or stochastic factors modify the penetrance of the cancerous mutant Tp53 phenotype. To test this possibility, this study explored dominant genetic modifiers of Tp53 mutations in heterozygous mice with different genetic backgrounds. Both genetic and stochastic effects upon tumor formation were observed in these mice. The genetic background of mice carrying Tp53 mutations has a strong influence upon the tissue type of the tumor produced and the number of tumors formed in a single mouse. The onset age of a tumor is correlated with the tissue type of that tumor, although identical tumor tissue types can occur at very different ages. These observations help to explain the great diversity of cancers in different Li-Fraumeni patients over lifetimes.

Links

 J:305009 – MGI References
33376133 – National Library of Medicine/PubMed

Strain Notes

Strain Note
(129S1/SvImJ x C57BL/6)F1-Trp53tm3.1Glo/+ These mice were generated by crossing female 129S1/SvImJ mice from the Jackson Laboratory (Stock #002448) with male homozygous mutant mice on a C57BL/6 genetic background.
(A/J x C57BL/6)F1-Trp53tm3.1Glo/+ These mice were generated by crossing female A/J mice from the Jackson Laboratory (Stock #000646) with male homozygous mutant mice on a C57BL/6 genetic background.
(BALB/cByJ x C57BL/6)F1-Trp53tm3.1Glo/+ These mice were generated by crossing female BALB/cByJ mice from the Jackson Laboratory (Stock #001026) with male homozygous mutant mice on a C57BL/6 genetic background.
(C3H/HeJ x C57BL/6)F1-Trp53tm3.1Glo/+ These mice were generated by crossing female C3H/HeJ mice from the Jackson Laboratory (Stock #000659) with male homozygous mutant mice on a C57BL/6 genetic background.
(DBA/1J x C57BL/6)F1-Trp53tm3.1Glo/+ These mice were generated by crossing female DBA/1J mice from the Jackson Laboratory (Stock #000670) with male homozygous mutant mice on a C57BL/6 genetic background.
(NOD/ShiLtJ x C57BL/6)F1-Trp53tm3.1Glo/+ These mice were generated by crossing female NOD/ShiLtJ mice from the Jackson Laboratory (Stock #001976) with male homozygous mutant mice on a C57BL/6 genetic background.
(SWR/J x C57BL/6)F1-Trp53tm3.1Glo/+ These mice were generated by crossing female SWR/J mice from the Jackson Laboratory (Stock #000689) with male homozygous mutant mice on a C57BL/6 genetic background.
Visual Summary Grid

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
(129S1/SvImJ x C57BL/6)F1-Trp53tm3.1Glo/+ Adipose tissue tumor Adipose tissue

2
(A/J x C57BL/6)F1-Trp53tm3.1Glo/+ Adipose tissue tumor Adipose tissue

20
(BALB/cByJ x C57BL/6)F1-Trp53tm3.1Glo/+ Adipose tissue tumor Adipose tissue

0
(C3H/HeJ x C57BL/6)F1-Trp53tm3.1Glo/+ Adipose tissue tumor Adipose tissue

0
(DBA/1J x C57BL/6)F1-Trp53tm3.1Glo/+ Adipose tissue tumor Adipose tissue

4
(NOD/ShiLtJ x C57BL/6)F1-Trp53tm3.1Glo/+ Adipose tissue tumor Adipose tissue

0
(SWR/J x C57BL/6)F1-Trp53tm3.1Glo/+ Adipose tissue tumor Adipose tissue

0
(129S1/SvImJ x C57BL/6)F1-Trp53tm3.1Glo/+ Blood vessel hemangioma Blood vessel

2
(A/J x C57BL/6)F1-Trp53tm3.1Glo/+ Blood vessel hemangioma Blood vessel

0
(BALB/cByJ x C57BL/6)F1-Trp53tm3.1Glo/+ Blood vessel hemangioma Blood vessel

2
(C3H/HeJ x C57BL/6)F1-Trp53tm3.1Glo/+ Blood vessel hemangioma Blood vessel

0
(DBA/1J x C57BL/6)F1-Trp53tm3.1Glo/+ Blood vessel hemangioma Blood vessel

4
(NOD/ShiLtJ x C57BL/6)F1-Trp53tm3.1Glo/+ Blood vessel hemangioma Blood vessel

3
(SWR/J x C57BL/6)F1-Trp53tm3.1Glo/+ Blood vessel hemangioma Blood vessel

1
(129S1/SvImJ x C57BL/6)F1-Trp53tm3.1Glo/+ Bone osteosarcoma Bone

6
(A/J x C57BL/6)F1-Trp53tm3.1Glo/+ Bone osteosarcoma Bone

17
(BALB/cByJ x C57BL/6)F1-Trp53tm3.1Glo/+ Bone osteosarcoma Bone

11
(C3H/HeJ x C57BL/6)F1-Trp53tm3.1Glo/+ Bone osteosarcoma Bone

8
(DBA/1J x C57BL/6)F1-Trp53tm3.1Glo/+ Bone osteosarcoma Bone

4
(NOD/ShiLtJ x C57BL/6)F1-Trp53tm3.1Glo/+ Bone osteosarcoma Bone

16
(SWR/J x C57BL/6)F1-Trp53tm3.1Glo/+ Bone osteosarcoma Bone

20
(129S1/SvImJ x C57BL/6)F1-Trp53tm3.1Glo/+ Leukocyte lesion Leukocyte

10
(A/J x C57BL/6)F1-Trp53tm3.1Glo/+ Leukocyte lesion Leukocyte

10
(BALB/cByJ x C57BL/6)F1-Trp53tm3.1Glo/+ Leukocyte lesion Leukocyte

4
(C3H/HeJ x C57BL/6)F1-Trp53tm3.1Glo/+ Leukocyte lesion Leukocyte

23
(DBA/1J x C57BL/6)F1-Trp53tm3.1Glo/+ Leukocyte lesion Leukocyte

21
(NOD/ShiLtJ x C57BL/6)F1-Trp53tm3.1Glo/+ Leukocyte lesion Leukocyte

24
(SWR/J x C57BL/6)F1-Trp53tm3.1Glo/+ Leukocyte lesion Leukocyte

30
(129S1/SvImJ x C57BL/6)F1-Trp53tm3.1Glo/+ Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

0
(A/J x C57BL/6)F1-Trp53tm3.1Glo/+ Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

7
(BALB/cByJ x C57BL/6)F1-Trp53tm3.1Glo/+ Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

4
(C3H/HeJ x C57BL/6)F1-Trp53tm3.1Glo/+ Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

4
(DBA/1J x C57BL/6)F1-Trp53tm3.1Glo/+ Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

0
(NOD/ShiLtJ x C57BL/6)F1-Trp53tm3.1Glo/+ Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

8
(SWR/J x C57BL/6)F1-Trp53tm3.1Glo/+ Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

4
(129S1/SvImJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) adenocarcinoma (Unspecified organ)

2
(A/J x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) adenocarcinoma (Unspecified organ)

3
(BALB/cByJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) adenocarcinoma (Unspecified organ)

13
(C3H/HeJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) adenocarcinoma (Unspecified organ)

4
(DBA/1J x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) adenocarcinoma (Unspecified organ)

7
(NOD/ShiLtJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) adenocarcinoma (Unspecified organ)

3
(SWR/J x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) adenocarcinoma (Unspecified organ)

11
(129S1/SvImJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) carcinoma (Unspecified organ)

2
(A/J x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) carcinoma (Unspecified organ)

0
(BALB/cByJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) carcinoma (Unspecified organ)

6
(C3H/HeJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) carcinoma (Unspecified organ)

0
(DBA/1J x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) carcinoma (Unspecified organ)

0
(NOD/ShiLtJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) carcinoma (Unspecified organ)

1
(SWR/J x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) carcinoma (Unspecified organ)

8
(129S1/SvImJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) tumor (Unspecified organ)

2 - 38
(A/J x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) tumor (Unspecified organ)

3 - 69
(BALB/cByJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) tumor (Unspecified organ)

15 - 80
(C3H/HeJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) tumor (Unspecified organ)

0 - 70
(DBA/1J x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) tumor (Unspecified organ)

4 - 47
(NOD/ShiLtJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) tumor (Unspecified organ)

1 - 65
(SWR/J x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) tumor (Unspecified organ)

4 - 96
(A/J x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) tumor - malignant (Unspecified organ)

87
(NOD/ShiLtJ x C57BL/6)F1-Trp53tm3.1Glo/+ (Unspecified organ) tumor - malignant (Unspecified organ)

69