Insight versus Quagmire with Compound HIV Transgenics

Abstract

“ Why don't you mate mouse X with mouse Y and see what happens? ” How many times has one heard that bit of advice? For the beleaguered postdoc assigned to this experiment, the undoubted conclusion will be: Talk is cheap. Actually completing this experiment is expensive, labor-intensive, and time-consuming. The popularity of transgenic cross-breeding studies stems from the wide availability of numerous existing transgenic lines, but mostly, it is the lure of the definitive in vivo experiment. On the one hand, most definitive experiments usually are difficult and time-consuming. On the other hand, many investigators would argue that transgenic cross-breeding studies, whether it be by folly, naivete, or bad luck, can be inadequately performed, making statistically significant data collection and interpretation of results challenging. With regard to the study of HIV-associated nephropathy (HIVAN), transgenic studies have been useful in illuminating aspects of pathogenesis; however, the literature is laden with countervailing reports from independent laboratories,1 leaving both readers and investigators struggling to find a consensus. The report by Feng et al. 2 in this issue of JASN was an opportunity to test definitively in vivo the well-developed hypothesis that HIVAN is caused by a virus-induced activation of the transcription factor STAT3. Current evidence suggests HIVAN is caused by HIV-1 infection of renal cells, and extensive in vitro work links several of the viral proteins, such as Nef and Vpr, …