HAPLOID MALE GERM CELLS SHOW NO SUSCEPTIBILITY TO TRANSFORMATION BY SIMIAN VIRUS 40 LARGE TUMOUR ANTIGEN IN TRANSGENIC MICE

1998 ◽  
Vol 22 (6) ◽  
pp. 437-443 ◽  
Author(s):  
K NAYERNIA
1994 ◽  
Vol 14 (10) ◽  
pp. 6743-6754 ◽  
Author(s):  
L Fromm ◽  
W Shawlot ◽  
K Gunning ◽  
J S Butel ◽  
P A Overbeek

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.


1991 ◽  
Vol 11 (12) ◽  
pp. 5968-5976
Author(s):  
J D Chen ◽  
T Van Dyke

The simian virus 40 (SV40) large tumor antigen (T antigen) under its natural regulatory elements induces choroid plexus papillomas in transgenic mice. Because these tumors develop focally after several months, it has been suggested that secondary cellular alterations are required to induce a tumor in this tissue. In contrast to SV40, the related lymphotropic papovavirus early region induces rapid nonfocal choroid plexus neoplasia in transgenic mice. Here, using hybrid gene constructs, we showed that T antigen from either virus in in fact sufficient to induce these tumors. Their abilities to induce proliferative abnormalities in other tissues, such as kidney and thymus, were also indistinguishable. Differences in the rate of choroid plexus tumorigenesis reflected differences in the control regions of the two viruses, rather than differences in T antigen per se. Under SV40 regulation, expression was limited to a fraction of the choroid plexus cells prior to the formation of focal tumors. When SV40 T antigen was placed under lymphotropic papovavirus control, in contrast, expression was generally uniform in the choroid plexus and rapid expansion of the tissue ensued. We found a direct relationship between T-antigen expression, morphological transformation, and proliferation of the choroid plexus epithelial cells. Analysis of mosaic transgenic mice indicated further that T antigen exerts its mitogenic effect cell autonomously. These studies form the foundation for elucidating the role of various T-antigen subactivities in tumorigenesis.


Virology ◽  
1992 ◽  
Vol 190 (1) ◽  
pp. 459-464 ◽  
Author(s):  
Satvir S. Tevethia ◽  
Melanie Epler ◽  
Ingo Georgoff ◽  
Angie Teresky ◽  
Marty Marlow ◽  
...  

genesis ◽  
2008 ◽  
Vol 46 (12) ◽  
pp. 738-742 ◽  
Author(s):  
Patricia I. Sadate-Ngatchou ◽  
Christopher J. Payne ◽  
Andrea T. Dearth ◽  
Robert E. Braun

1994 ◽  
Vol 266 (6) ◽  
pp. G987-G1003 ◽  
Author(s):  
P. Falk ◽  
K. A. Roth ◽  
J. I. Gordon

We have used histochemical methods to survey the cellular patterns of binding of a panel of 45 lectins with well-defined carbohydrate specificities to sections prepared from various regions of the gastric-to-colonic axis of fetal, neonatal, and adult FVB/N mouse gut. The results suggest that lectins can be used as remarkably sensitive tools to describe the differentiation programs of gastric and intestinal epithelial cell lineages as a function of their position along the cephalocaudal axis of the gut and as a function of developmental stage. Studies of intestinal isografts and transgenic mice that express Simian virus-40 T antigen in enterocytes suggest that many of these cell lineage-specific and spatial patterns of glycoconjugate production can be established and maintained in the absence of exposure to luminal contents and in the presence of specific proliferative abnormalities. This lectin panel should be useful for operationally defining subpopulations of the principal gut epithelial cell lineages in normal strains of mice, for describing variations in gut epithelial cell differentiation programs in mutant and transgenic mice, and for recovering specific epithelial cell lineages or subpopulations.


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