Reference SummaryLanduzzi L, Oncotarget 2014 Dec 15;5(23):11924-38

Title

 Genetic prevention of lymphoma in p53 knockout mice allows the early development of p53-related sarcomas.

Authors

 Landuzzi L; Ianzano ML; Nicoletti G; Palladini A; Grosso V; Ranieri D; Dall'Ora M; Raschi E; Laranga R; Gambarotti M; Picci P; De Giovanni C; Nanni P; Lollini PL

Journal

 Oncotarget

Volume

 5

Issue

 23

Year

 2014

Pages

 11924-38

Abstract

 Homozygous knockout of p53 in mice leads to early mortality from lymphoma, with almost complete penetrance, thus hampering studies of other tumor histotypes related to p53 alterations. To avoid lymphoma development, we crossed p53 knockout mice (BALB-p53 mice) with alymphocytic BALB/c Rag2-/-;Il2rg-/- (RGKO) mice. We compared the tumor spectrum of homozygous (BALB-p53-/-) and heterozygous (BALB-p53+/-) mice with alymphocytic mice (RGKO-p53-/- and RGKO-p53+/-). Lymphoma incidence in BALB-p53-/- mice exceeded 80%, whereas in RGKO-p53-/- it was strongly reduced. The prevalent tumor of RGKO-p53-/- mice was hemangiosarcoma (incidence over 65% in both sexes, mean latency 18 weeks), other tumors included soft tissue sarcomas (incidence ~10%), lung and mammary carcinomas. Tumor spectrum changes occurred also in p53 heterozygotes, in which lymphomas are relatively rare (~20%). RGKO-p53+/- had an increased incidence of hemangiosarcomas, reaching ~30%, and females had an increased incidence of osteosarcomas, reaching ~20%. Osteosarcomas shared with the corresponding human tumors the involvement of limbs and a high metastatic ability, mainly to the lungs. Specific alterations in the expression of p53-related genes (p16Ink4a, p19Arf, p15Ink4b, p21Cip1) were observed. Genetic prevention of lymphoma in p53 knockout mice led to new models of sarcoma development, available for studies on hemangiosarcoma and osteosarcoma onset and metastatization.

Links

 J:307199 – MGI References
25426555 – National Library of Medicine/PubMed

Strain Notes

Strain Note
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj These mice were generated by mutiple crosses using C.129S2(B6)-Trp53tm1Tyj/J mice, C.129-Il2rgtm1Sug Rag2tm1Fwa mice, and the resulting offspring.
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj/+ These mice were generated by mutiple crosses using C.129S2(B6)-Trp53tm1Tyj/J mice, C.129-Il2rgtm1Sug Rag2tm1Fwa mice, and the resulting offspring.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C.129S2(B6)-Trp53tm1Tyj/J Blood vessel hemangiosarcoma Blood vessel

25 - 26
C.129S2(B6)-Trp53tm1Tyj/J Blood vessel hemangiosarcoma Blood vessel

0 - 9.1
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Blood vessel hemangiosarcoma Blood vessel

65 - 86
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Blood vessel hemangiosarcoma Skin

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Blood vessel hemangiosarcoma Muscle

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Blood vessel hemangiosarcoma Liver

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Blood vessel hemangiosarcoma Lung

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Blood vessel hemangiosarcoma Peritoneum

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Blood vessel hemangiosarcoma Intestine

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Blood vessel hemangiosarcoma Spleen

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Blood vessel hemangiosarcoma Urogenital tract (sex not specified)

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj/+ Blood vessel hemangiosarcoma Blood vessel

12.5 - 29
C.129S2(B6)-Trp53tm1Tyj/J Bone osteosarcoma Bone

0 - 9.7
C.129S2(B6)-Trp53tm1Tyj/J Bone osteosarcoma Bone

3.0 - 9.1
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Bone osteosarcoma Bone

0
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj/+ Bone osteosarcoma Limb

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj/+ Bone osteosarcoma Bone

7.3 - 19
C.129S2(B6)-Trp53tm1Tyj/J Leukocyte lymphoma Leukocyte

74 - 84
C.129S2(B6)-Trp53tm1Tyj/J Leukocyte lymphoma Thymus

observed
C.129S2(B6)-Trp53tm1Tyj/J Leukocyte lymphoma Leukocyte

12 - 27
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Leukocyte lymphoma Thymus

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Leukocyte lymphoma Leukocyte

12 - 14
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj/+ Leukocyte lymphoma Leukocyte

3.1 - 4.9
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Lung carcinoma Lung

observed
C.129S2(B6)-Trp53tm1Tyj/J Mammary gland carcinoma Mammary gland

0 - 6.5
C.129S2(B6)-Trp53tm1Tyj/J Mammary gland carcinoma Mammary gland

0 - 64
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Mammary gland carcinoma Mammary gland

observed - 9.5
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj/+ Mammary gland carcinoma Mammary gland

9.8 - 52
C.129S2(B6)-Trp53tm1Tyj/J Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

82
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj Pericyte hemangiopericytoma Limb - Forelimb

observed
C.129S2(B6)-Trp53tm1Tyj/J (Unspecified organ) carcinoma (Unspecified organ)

observed
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj (Unspecified organ) carcinoma (Unspecified organ)

34
C.129S2(B6)-Trp53tm1Tyj/J (Unspecified organ) sarcoma (Unspecified organ)

3.1 - 9.7
C.129S2(B6)-Trp53tm1Tyj/J (Unspecified organ) sarcoma (Unspecified organ)

6.0 - 9.1
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj (Unspecified organ) sarcoma (Unspecified organ)

12 - 14
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj/+ (Unspecified organ) sarcoma (Unspecified organ)

1.6 - 4.9
C.129S2(B6)-Trp53tm1Tyj/J (Unspecified organ) tumor (Unspecified organ)

6.25 - 100
C.129S2(B6)-Trp53tm1Tyj/J (Unspecified organ) tumor (Unspecified organ)

21 - 100
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj (Unspecified organ) tumor (Unspecified organ)

29 - 100
BALB/c-Il2rgtm1Sug Ragtm1Fwa Trp53tm1Tyj/+ (Unspecified organ) tumor (Unspecified organ)

37.5 - 100