Reference SummaryDuddy SK, Toxicol Appl Pharmacol 1999 Apr 15;156(2):106-12

Title	p53 is not inactivated in B6C3F1 mouse vascular tumors arising spontaneously or associated with long-term administration of the thiazolidinedione troglitazone.
Authors	Duddy SK; Parker RF; Bleavins MR; Gough AW; Rowse PE; Gorospe S; Dethloff LA; de la Iglesia FA
Journal	Toxicol Appl Pharmacol
Volume	156
Issue	2
Year	1999
Pages	106-12
Abstract	Hemangiomas and hemangiosarcomas are uncommon in rodents and humans and, as such, the mechanisms giving rise to these tumors are poorly understood. Inactivating mutations in the p53 gene have been detected in sporadic and chemically induced human and rodent hemangiosarcomas. Additionally, experimental ablation of p53 function in mice by targeted gene disruption increases the incidence of both spontaneous and carcinogen-induced vascular tumors. These findings implicate p53 disruption in vascular tumor development. In this study, we characterized p53 inactivation immunocytochemically and by gene sequencing in a large number of vascular tumors that developed in B6C3F1 mice during a long-term (2-year) study of the thiazolidinedione troglitazone. For comparative purposes, a murine hemangiosarcoma induced by polyoma middle-T antigen, which transforms endothelial cells via a p53-independent mechanism, five spontaneous human hemangiosarcoma specimens, and species-specific positive control tissues were also evaluated by immunocytochemistry for p53 inactivation. While 20% of the human hemangiosarcomas and all positive control tissues expressed significant levels of nuclear p53, indicating functional inactivation of the protein, none of the 161 mouse vascular tumors studied expressed detectable p53 protein. The absence of inactivating mutations was confirmed in eight of the histologically most malignant mouse hemangiosarcomas by sequencing exons 5 to 8 of the p53 gene. These results demonstrate that p53 inactivation did not play a role in development of the vascular tumors seen in the long-term study of troglitazone, and they indicate that loss of p53 function is not essential for vascular tumor development in mice. Copyright 1999 Academic Press.
Links	J:55234 – MGI References 10198275 – National Library of Medicine/PubMed

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency	Model Details
(C57BL/6 x C3H)F1	Blood vessel hemangioma		Blood vessel	0 - 6.7
(C57BL/6 x C3H)F1	Blood vessel hemangioma	troglitazone	Blood vessel	1.7 - 8.3
(C57BL/6 x C3H)F1	Blood vessel hemangiosarcoma		Blood vessel	0 - 13
(C57BL/6 x C3H)F1	Blood vessel hemangiosarcoma	troglitazone	Blood vessel	observed - 27