We have previously designed a library of lentiviral vectors to generate somatic-transgenic rodents to monitor signalling pathways in diseased organs using whole-body bioluminescence imaging, in conscious, freely moving rodents. We have now expanded this technology to adeno-associated viral vectors. We first explored bio-distribution by assessing GFP expression after neonatal intravenous delivery of AAV8. We observed widespread gene expression in, central and peripheral nervous system, liver, kidney and skeletal muscle. next, we selected a constitutive SffV promoter and nfκB binding sequence for bioluminescence and biosensor evaluation. An intravenous injection of AAV8 containing firefly luciferase and eGFP under transcriptional control of either element resulted in strong and persistent widespread luciferase expression. A single dose of LPS-induced a 10-fold increase in luciferase expression in AAV8-NFκB mice and immunohistochemistry revealed Gfp expression in cells of astrocytic and neuronal morphology. Importantly, whole-body bioluminescence persisted up to 240 days. We have validated a novel biosensor technology in an AAV system by using an nfκB response element and revealed its potential to monitor signalling pathway in a non-invasive manner in a model of LPS-induced inflammation. This technology complements existing germline-transgenic models and may be applicable to other rodent disease models.Germline light-producing transgenic mice where luciferase expression is controlled by an endogenous promoter, a surrogate promoter or by a minimal promoter downstream of tandem, synthetic, transcription factor binding elements, are used to provide an in vivo readout of physiological and pathological processes 1,2 . One of the advantages of this technology is that every cell will contain a copy of the luciferase transgene and therefore provide a whole-body transgene expression profile under the control of a specific promoter of choice. However, producing germline transgenics requires frequent backcrossing and therefore becomes a time-consuming and costly process, using many rodents.We have previously developed a novel technology which allows the generation of light-producing somatic transgenic rodents, using lentiviral vectors as a proof-of-concept system 3 and have validated this technology both in vitro 4,5 and in vivo 1,6 . We have also demonstrated that signalling pathways in diseased organs can be monitored specifically, continually and in a non-invasive manner 1,2 . Exploiting the immune tolerance of neonatal mice