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Nonetheless, we continue to see children and adolescents with HIVAN all over the world. Furthermore, once HIVAN is established in children, it is difficult to revert its long-term progression, and we need better animal models of childhood HIVAN to test new treatments. To define whether the HIV-1 trans-activator (Tat) gene precipitates HIVAN in young mice, and to develop an inducible mouse model of childhood HIVAN, an HIV-Tat gene cloned from a child with HIVAN was used to generate recombinant adenoviral vectors (rAd-Tat). rAd-Tat and LacZ control vectors (2\u00d7109) were expressed in the kidney of newborn wild-type and HIV-transgenic (Tg26) FVB\/N mice without significant proteinuria (n=5; 8 per group). Mice were sacrificed 7 and 35\u2005days later to assess their renal outcome, the expression of HIV-genes and growth factors, and markers of cell growth and differentiation by RT-qPCR, immunohistochemistry and\/or western blots. HIV-Tat induced the expression of HIV-1 genes and heparin-binding growth factors in the kidney of HIV-Tg26 mice, and precipitated HIVAN in the first month of life. No significant renal changes were detected in wild-type mice infected with rAd-Tat vectors, suggesting that HIV-Tat alone does not induce renal disease. This new mouse model of childhood HIVAN highlights the critical role that HIV-Tat plays in the pathogenesis of HIVAN, and could be used to study the pathogenesis and treatment of HIVAN in children and adolescents.<\/jats:p>","DOI":"10.1242\/dmm.045641","type":"journal-article","created":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T12:50:17Z","timestamp":1599828617000},"source":"Crossref","is-referenced-by-count":5,"title":["An HIV-Tat inducible mouse model system of childhood HIV-associated nephropathy"],"prefix":"10.1242","volume":"13","author":[{"given":"Pingtao","family":"Tang","sequence":"first","affiliation":[{"name":"Center 1 \u2008 , Washington, DC 20010 , USA"},{"name":"for Genetic Medicine Research, Children's National Hospital 1 \u2008 , Washington, DC 20010 , USA"},{"name":"Department of Pediatrics, The George Washington University School of Medicine 2 , Washington , DC 20052 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jharna R.","family":"Das","sequence":"additional","affiliation":[{"name":"Center 1 \u2008 , Washington, DC 20010 , USA"},{"name":"for Genetic Medicine Research, Children's National Hospital 1 \u2008 , Washington, DC 20010 , USA"},{"name":"Department of Pediatrics, The George Washington University School of Medicine 2 , Washington , DC 20052 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinliang","family":"Li","sequence":"additional","affiliation":[{"name":"Center 1 \u2008 , Washington, DC 20010 , USA"},{"name":"for Genetic Medicine Research, Children's National Hospital 1 \u2008 , Washington, DC 20010 , USA"},{"name":"Department of Pediatrics, The George Washington University School of Medicine 2 , Washington , DC 20052 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yu","sequence":"additional","affiliation":[{"name":"Child Health Research Center 3 , Department of Pediatrics , , Charlottesville, VA 22908 , USA"},{"name":"University of Virginia School of Medicine 3 , Department of Pediatrics , , Charlottesville, VA 22908 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2223-9584","authenticated-orcid":false,"given":"Patricio E.","family":"Ray","sequence":"additional","affiliation":[{"name":"Child Health Research Center 3 , Department of Pediatrics , , Charlottesville, VA 22908 , USA"},{"name":"University of Virginia School of Medicine 3 , Department of Pediatrics , , Charlottesville, VA 22908 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,10,28]]},"reference":[{"key":"2024061302312529200_DMM045641C1","doi-asserted-by":"publisher","first-page":"F757","DOI":"10.1152\/ajprenal.1997.273.5.F757","article-title":"Ureteric bud cells secrete multiple factors, including bFGF, which rescue renal progenitors from apoptosis","volume":"273","author":"Barasch","year":"1997","journal-title":"Am. 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