title: Pathophysiology of vascular smooth muscle in renin promoter-T-antigen transgenic mice.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
authors.forename: C D
authors.initials: CD
authors.lastname: Sigmund
authors.forename: C A
authors.initials: CA
authors.lastname: Jones
authors.forename: H J
authors.initials: HJ
authors.lastname: Jacob
authors.forename: J
authors.initials: J
authors.lastname: Ingelfinger
authors.forename: U
authors.initials: U
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Gamble
authors.forename: V J
authors.initials: VJ
authors.lastname: Dzau
authors.forename: K W
authors.initials: KW
authors.lastname: Gross
mesh_terms: 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
chemical_list: D000957:Antigens, Viral, Tumor; D012333:RNA, Messenger; D002216:Captopril; D012083:Renin