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Studies on the pathology, especially brain lesions, induced by R7, a spontaneous mutant of Moloney murine sarcoma
1Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville 78957, USA.
Abstract:
We have recently isolated R7, a spontaneous Moloney murine sarcoma virus (MoMuSV) 124 variant. Molecular cloning and sequence analysis showed that, relative to MoMuSV 124, R7 has an extra repeat in each enhancer and a truncated mos gene in frame with the truncated gag coding sequence. This report presents a detailed study on the pathology induced by R7. R7 induced not only sarcomas with well developed angiomatous components but also brain lesions. Brain lesions were observed in all less-than-48-hour-old BALB/c mice inoculated with greater than 2 x 10(5) R7 focus-forming units (FFUs). R7 was detected in all brains examined by day 9 after inoculation, and brain lesions were observed in two of four mice examined by day 14 after inoculation. Light microscopy of brains revealed that approximately 15% of the lesions were unenclosed blood pools of varying sizes containing red blood cells and inflammatory cells spreading into surrounding brain tissues. The remainder of the brain lesions had tumor cells. These lesions ranged from a few enlarged vascular endothelial cells intermixed with blood cells to large circumscribed lesions consisting of well developed tangled masses of vessels surrounded by blood pools. Activated astrocytes surrounded and infiltrated the tumors. In addition, the thymus of R7-infected mice regressed significantly and precipitously due to apoptosis (especially of cortical thymocytes) at the end stage of the disease.
Insights
A Moloney murine sarcoma virus (MoMuSV) variant, R7, causes sarcomas and unique brain lesions in young mice. R7 also induces thymus regression through apoptosis in infected mice.
Area of Science:
- Virology
- Pathology
- Oncology
Background:
- Moloney murine sarcoma virus (MoMuSV) is a retrovirus known to induce tumors.
- A novel variant, R7, was isolated from MoMuSV 124.
Purpose of the Study:
- To investigate the pathological effects of the R7 variant.
- To characterize the induced sarcomas and brain lesions.
- To examine thymus alterations in R7-infected mice.
Main Methods:
- Molecular cloning and sequence analysis of the R7 variant.
- Pathological examination of R7-induced lesions in BALB/c mice.
- Histological analysis of brain and thymus tissues.
Main Results:
- R7 induced sarcomas with angiomatous components and significant brain lesions in young mice.
- Brain lesions included blood pools and vascular tumors with astrocyte infiltration.
- Significant and rapid thymus regression due to apoptosis was observed in R7-infected mice.
Conclusions:
- The R7 variant of MoMuSV possesses distinct pathogenic properties, inducing both sarcomas and specific brain pathologies.
- R7-induced brain lesions involve vascular abnormalities and inflammatory responses.
- Apoptosis-driven thymus regression is a feature of R7 infection, indicating systemic effects.