HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yokoyama, H. Articles by Iwakura, Y. Search for Related Content PubMed PubMed Citation Articles by Yokoyama, H. Articles by Iwakura, Y. Agricola Articles by Yokoyama, H. Articles by Iwakura, Y.

Pathological changes of renal epithelial cells in mice transgenic for the TT virus ORF1 gene

Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan¹
Division of Molecular Virology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan²
Immunology Division and Division of Molecular Virology, Jichi Medical School, Tochigi-Ken, Japan³

Author for correspondence: Yoichiro Iwakura. Fax +81 3 5449 5430. e-mail iwakura{at}ims.u-tokyo.ac.jp

TT virus (TTV) is a newly identified human DNA virus of the family Circoviridae. Its genome consists of six putative open reading frames (ORFs). TTV was isolated originally from a patient with cryptogenic hepatitis and the association of TTV with hepatitis has been studied extensively, while its significance in other diseases is unknown. To examine the pathogenicity of TTV, mice transgenic for the ORF genes in various combinations were produced. A total of 11 independent founder mice was produced: two mice, which were found to carry the ORF1 gene, showed pathological changes in the kidney; other tissues were not affected. In these mice, the transgene was expressed most strongly in the kidney and the transcript was shown to be spliced to encode a protamine-like, highly basic protein. Mice from a line with high transgene expression developed renal failure with severe renal epithelial cell abnormalities resembling those seen in humans with nephrotic syndrome. The transgenic mice with severe ascites died before reaching the age of 5 weeks. Another founder mouse with low expression levels also showed similar, but milder, renal epithelial cell changes, indicating that these effects were not caused by the insertion of the transgene, but, rather, were caused by the ORF1 gene product. These observations suggest that TTV affects renal epithelial cells as part of the naturally occurring infection.

This article has been cited by other articles:

				L. Leppik, K. Gunst, M. Lehtinen, J. Dillner, K. Streker, and E.-M. de Villiers In Vivo and In Vitro Intragenomic Rearrangement of TT Viruses J. Virol., September 1, 2007; 81(17): 9346 - 9356. [Abstract] [Full Text] [PDF]

				F. Maggi, M. Pifferi, C. Fornai, E. Andreoli, E. Tempestini, M. Vatteroni, S. Presciuttini, S. Marchi, A. Pietrobelli, A. Boner, et al. TT Virus in the Nasal Secretions of Children with Acute Respiratory Diseases: Relations to Viremia and Disease Severity J. Virol., February 15, 2003; 77(4): 2418 - 2425. [Abstract] [Full Text] [PDF]