Development of Transgenic Mice Expressing a Conditionally Active Form of the eIF2α Kinase PKR

Phosphorylation of the alpha (alpha) subunit of the eukaryotic initiation factor 2 (eIF2) at serine 51 is an important mechanism of translational control in response to various forms of environmental stress. In metazoans, eIF2 alpha phosphorylation is mediated by four kinases each of which becomes activated by distinct stimuli. Previous work established that expression of a chimera protein comprising of the bacteria Gyrase B N-terminal (GyrB) domain fused to the kinase domain (KD) of the eIF2 alpha kinase PKR is capable of inducing eIF2 alpha phosphorylation in cultured cells after treatment with the antibiotic coumermycin. Herein, we report the development of transgenic mice expressing the fusion protein GyrB. PKR ubiquitously. Treatment of mice with coumermycin induces eIF2 alpha phosphorylation in vivo as demonstrated by immunoblotting and immunoshisto-chemistry of mouse tissues. The GyrB. PKR transgene represents a useful model system to investigate the biological effects of the conditional induction of eIF2 alpha phosphorylation in vivo in the absence of parallel signaling pathways that are elicited in response to stress. genesis 49: 743-749, 2011. (C) 2011 Wiley-Liss, Inc.