Targeted expression of SV40 large tumour antigen (TAg) induces a transient enhancement of spermatocyte proliferation and apoptosis.
In an attempt to determine the susceptibility of spermatocytes to malignant transformation by simian virus 40 (SV40) large tumour antigen (TAg), transgenic mice harbouring a chimeric gene composed of the SV40 TAg gene fused to the 1.4 kb promoter sequence of the human phosphoglycerate kinase 2 (PGK2) gene were generated. Northern blot analysis on RNA from different tissues indicated a specific transcription of TAg in the testis of PGK2-TAg transgenic mice. Reverse transcription-polymerase chain reaction and Western blot analysis on testes at different stages of development revealed that transcription and translation of the TAg gene starts in 12-day-old testis, which coincides with the appearance of pre-leptotene spermatocytes. Germ cells of transgenic mice showed no tendency toward transformation, but in testes of both 18- and 25-day-old transgenic mice, a significantly enhanced number of spermatocytes was found. In contrast, in 42-day-old transgenic mice no differences in the number of spermatocytes and spermatids were observed. The number of Sertoli cells was determined to be equal in transgenic and wild type mice. In-situ end labelling of fragmented DNA revealed a higher rate of apoptosis in testes of 18-day-old transgenic mice as compared with wild type mice. These results indicate that germ cell homeostasis in transgenic mice is maintained by an apoptotic mechanism.
Tascou
S
S
Institute of Human Genetics, University of Göttingen, Heinrich Dücker Weg 1237073 Göttingen, Germany.
Nayernia
K
K
Meinhardt
A
A
Schweyer
S
S
Engel
W
W
Trappe
R
R
Burfeind
P
P
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D019677:Artificial Gene Fusion; D002454:Cell Differentiation; D017930:Genes, Reporter; D006801:Humans; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010735:Phosphoglycerate Kinase / Q000235:genetics; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins; D013539:Simian virus 40 / Q000276:immunology*; D013090:Spermatocytes / Q000502:physiology*; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology / Q000502:physiology*; D014170:Transformation, Genetic
D000952:Antigens, Polyomavirus Transforming; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D010735:Phosphoglycerate Kinase; C104317:phosphoglycerate kinase, testis specific