Transgenic Mouse Strategies in Virus Research

Abstract

The use of viruses and viral genes for infection and microinjection experiments with mouse embryos has greatly contributed to the development of transgenic technologies. Likewise, these techniques have proved very useful in providing insights into basic aspects of virus research, specially into those related to viral pathogenesis and virus-host interactions. Indeed, an impressive number of studies involving transgenic mice carrying viral sequences have been reported during the past 10 years (nearly 900 records can be retrieved from the Medline databases under the entries transgenic mouse and virus). The following is a summary of the main topics on virus research using transgenic mice, including some illustrative references:

• Studies on the oncogenic activity of viral proteins (see for review Adams and Cory 1991; Merlino 1994). Oncogenes of the so-called tumor viruses (zur Hausen 1991) have been expressed in mouse tissues from either homologous or heterologous viral control regions, or with the help of eukaryotic promoters. In the latter case, promoters of genes expressed selectively in specific tissues have been preferred. Thus, for instance, the α-A crystallin promoter and the keratin 10 promoters have been used to target transgene expression to lens and skin, respectively (e.g., Griep et al. 1993; Auewarakul et al. 1994). In some cases, two or more viral oncogenes were combined in transgenic mice for studies on oncogene cooperation (e.g., van Lohuizen et al. 1991; see also Berns 1991), as was done previously in studies in vitro. In addition, transgenes containing tissue-specific promoters fused to viral oncogenes (most frequently the SV40 large T-antigen), have been used to assess many aspects of tumorigenesis, apoptosis, and cell cycle control. Recently, male germ cells have been reported to undergo trans-meiotic differentiation in vitro by expression of the SV40 large T-antigen (see Rassoulzadegan et al., Chap. 12, this Vol.).