scholarly journals Renal cyst formation and multifocal neoplasia in transgenic mice carrying the simian virus 40 early region.

1991 ◽  
Vol 2 (1) ◽  
pp. 84-97
Author(s):  
K A Kelley ◽  
N Agarwal ◽  
S Reeders ◽  
K Herrup
Keyword(s):  
Transgenic Mice ◽  
Renal Cyst ◽  
Simian Virus 40 ◽  
Antigen Expression ◽  
Simian Virus ◽  
T Antigen ◽  
Tumor Formation ◽  
Large T Antigen ◽  
Early Region ◽  
The Brain

Simian virus 40 early region transgenic mice develop characteristic pathological abnormalities of the brain, kidney, and thymus, due to expression of large-T antigen. Earlier studies have indicated that the most consistent effect of large-T antigen expression is the formation of choroid plexus papillomas in the brain and that thymic hyperplasia and various kidney abnormalities are less frequently observed. The renal lesions reportedly consist of numerous glomerular abnormalities and tubular proliferation. Surprisingly, an analysis of 21 simian virus 40 early region transgenic mice, which were produced for this study, revealed a much higher incidence of polycystic kidney disease as well as earlier development of T-antigen-induced abnormalities. In marked contrast to earlier observations, there is an apparent reduction in the glomerular number in the affected kidneys, whereas the remaining glomeruli appear normal. The most striking feature of the T-antigen-induced renal abnormalities was extensive hyperplasia of tubular epithelial cells which was most marked in the distal tubules; all tubule segments are involved in the most severely affected animals. In most cases, cysts lined with hyperplastic epithelium were observed and papillary structures protruding from the cyst lining were evident. Multiple areas of focal neoplasia were apparent, and, in the most severely affected animals, there were areas in which tumor had replaced normal renal parenchyma. These results strongly suggest that T-antigen-induced renal cyst and tumor formation are part of the same pathological process which is initially manifested as tubular epithelial hyperplasia.

scholarly journals The retinoblastoma protein-binding region of simian virus 40 large T antigen alters cell cycle regulation in lenses of transgenic mice.

1994 ◽  
Vol 14 (10) ◽  
pp. 6743-6754 ◽  
Author(s):  
L Fromm ◽  
W Shawlot ◽  
K Gunning ◽  
J S Butel ◽  
P A Overbeek
Keyword(s):  
Cell Cycle ◽  
Transgenic Mice ◽  
Retinoblastoma Protein ◽  
Simian Virus 40 ◽  
Cell Types ◽  
Simian Virus ◽  
T Antigen ◽  
Lens Fiber ◽  
Large T Antigen ◽  
Fiber Cells

Regulation of the cell cycle is a critical aspect of cellular proliferation, differentiation, and transformation. In many cell types, the differentiation process is accompanied by a loss of proliferative capability, so that terminally differentiated cells become postmitotic and no longer progress through the cell cycle. In the experiments described here, the ocular lens has been used as a system to examine the role of the retinoblastoma protein (pRb) family in regulation of the cell cycle during differentiation. The ocular lens is an ideal system for such studies, since it is composed of just two cell types: epithelial cells, which are capable of proliferation, and fiber cells, which are postmitotic. In order to inactivate pRb in viable mice, genes encoding either a truncated version of simian virus 40 large T antigen or the E7 protein of human papillomavirus were expressed in a lens-specific fashion in transgenic mice. Lens fiber cells in the transgenic mice were found to incorporate bromodeoxyuridine, implying inappropriate entry into the cell cycle. Surprisingly, the lens fiber cells did not proliferate as tumor cells but instead underwent programmed cell death, resulting in lens ablation and microphthalmia. Analogous lens alterations did not occur in mice expressing a modified version of the truncated T antigen that was mutated in the binding domain for the pRb family. These experimental results indicate that the retinoblastoma protein family plays a crucial role in blocking cell cycle progression and maintaining terminal differentiation in lens fiber cells. Apoptotic cell death ensues when fiber cells are induced to remain in or reenter the cell cycle.

scholarly journals Expression of simian virus 40 large T antigen in embryonal carcinoma cell hybrids.

1984 ◽  
Vol 4 (8) ◽  
pp. 1657-1660 ◽  
Author(s):  
A Tunnacliffe ◽  
L V Crawford ◽  
P Goodfellow
Keyword(s):  
Embryonal Carcinoma ◽  
Carcinoma Cell ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Carcinoma Cells ◽  
Embryonal Carcinoma Cell ◽  
Embryonal Carcinoma Cells ◽  
Large T Antigen ◽  
Early Region

Previous work has shown that murine embryonal carcinoma cells are refractory to infection with various viruses, including simian virus 40. Thus, large T and small t antigens, the products of the simian virus 40 early region, are not produced when the virus infects embryonal carcinoma cells, in contrast to other cell types. We show, by qualitative and quantitative analyses, that embryonal carcinoma cell hybrids, containing a simian virus 40 early region integrated into human DNA, are capable of producing viral large T antigen.

scholarly journals Intestinal Dysplasia Induced by Simian Virus 40 T Antigen Is Independent of p53

2005 ◽  
Vol 79 (12) ◽  
pp. 7492-7502 ◽  
Author(s):  
Jennifer A. Markovics ◽  
Patrick A. Carroll ◽  
M. Teresa Sáenz Robles ◽  
Hannah Pope ◽  
Craig M. Coopersmith ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Kinase Inhibitor ◽  
Simian Virus 40 ◽  
Antigen Expression ◽  
Simian Virus ◽  
T Antigen ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Tumor Suppressor Proteins ◽  
Intestinal Hyperplasia

ABSTRACT Transgenic mice expressing simian virus 40 large T antigen in enterocytes develop intestinal hyperplasia that progresses to dysplasia with age. Hyperplasia is dependent on T antigen binding to the retinoblastoma (pRb) family of tumor suppressor proteins. Mice expressing a truncated T antigen that inactivates the pRb-family, but is defective for binding p53, exhibit hyperplasia but do not progress to dysplasia. We hypothesized that the inhibition of the pRb family leads to entry of enterocytes into the cell cycle, resulting in hyperplasia, while inactivation of p53 is required for progression to dysplasia. Therefore, we examined T antigen/p53 complexes from the intestines of transgenic mice. We found that T antigen did not induce p53 stabilization, and we could not detect T antigen/p53 complexes in villus enterocytes. In contrast, T antigen expression led to a large increase in the levels of the cyclin-dependent kinase inhibitor p21. Furthermore, mice in which pRb was inactivated by a truncated T antigen in a p53 null background exhibited intestinal hyperplasia but no progression to dysplasia. These data indicate that loss of p53 function does not play a role in T antigen-induced dysplasia in the intestine. Rather, some unknown function of T antigen is essential for progression beyond hyperplasia.

scholarly journals Haploid-specific transcription of protamine-myc and protamine-T-antigen fusion genes in transgenic mice.

1988 ◽  
Vol 8 (4) ◽  
pp. 1748-1755 ◽  
Author(s):  
T A Stewart ◽  
N B Hecht ◽  
P G Hollingshead ◽  
P A Johnson ◽  
J A Leong ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Fusion Gene ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Fusion Genes ◽  
Sv40 T Antigen ◽  
Early Region ◽  
Myc Gene ◽  
Sv40 Early Region

The protamines are small, basic, arginine-rich proteins synthesized postmeiotically in the testes. Analysis of the regulation of synthesis of the protamine mRNA and protein is restricted by the difficulty in culturing and manipulating the cells in which transcription and translation occur. To avoid these problems, we have produced transgenic mice carrying fusion genes in which sequences 5' to the mouse protamine-2 gene have been linked to exons 2 and 3 of the mouse c-myc gene and, separately, to the simian virus 40 (SV40) early region. We show here that the prot.myc gene is correctly regulated; transcription is detected only in the round spermatids. In one family of transgenic mice carrying the 5' protamine-SV40 T-antigen fusion gene, SV40 early-region mRNA accumulated to the highest level in the testes but was also detected in the thymuses, brains, hearts, and preputial glands of the animals. Although we have demonstrated specific transcription of these fusion genes in the round spermatids, we were not able to detect the SV40 T-antigen protein.

Establishment of a novel chondrocyte-like cell line derived from transgenic mice harboring the temperature-sensitive simian virus 40 large T-antigen gene

2009 ◽  
Vol 11 (11) ◽  
pp. 1646-1654 ◽  
Author(s):  
Nobuko Mataga ◽  
Masato Tamura ◽  
Nobuyuki Yanai ◽  
Tamayuki Shinomura ◽  
Koji Kimata ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cell Line ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Temperature Sensitive ◽  
Large T Antigen ◽  
Antigen Gene
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