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.