Pathophysiology of vascular smooth muscle in renin promoter-T-antigen transgenic mice.
The pathophysiological consequence of targeted production of SV-40 T-antigen to renin-expressing cells in the kidney of transgenic mice is reported. A histopathologic analysis of the kidney from adult transgenic mice (12-16 wk old) revealed the presence of severe vascular lesions manifested by marked atypical hyperplasia of vascular smooth muscle. The levels of plasma renin, kidney renin, and kidney renin mRNA were examined in 6- and 9-wk-old transgenic mice and were found to be significantly lower than their age-matched non-transgenic littermates and were nonresponsive to captopril treatment. However, there was no significant difference in conscious mean arterial pressure between transgenic and non-transgenic mice. The levels of renal renin mRNA in transgenics and nontransgenic littermates were compared throughout ontogeny and were found to be equal in newborns, elevated 3- to 5-fold in 1-wk-old transgenics, and yet decreased 10-fold by 6 wk of age in transgenic mice. Expression of the transgene in the kidney exhibited the proper developmental pattern and was properly restricted to juxtaglomerular cells in neonatal mice. Nevertheless, in adult mice, T-antigen-containing cells were found throughout the entire renal arterial tree. The observed ability of renal vascular cells to be recruited to express both renin and T-antigen suggests a mechanism that can explain the development of the renal pathology in these mice.
Sigmund
C D
CD
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Jones
C A
CA
Jacob
H J
HJ
Ingelfinger
J
J
Kim
U
U
Gamble
D
D
Dzau
V J
VJ
Gross
K W
KW
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics*; D001794:Blood Pressure; D002216:Captopril / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012083:Renin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution
D000957:Antigens, Viral, Tumor; D012333:RNA, Messenger; D002216:Captopril; D012083:Renin