RT Journal Article SR Electronic T1 Generation of light-producing somatic-transgenic mice using adeno-associated virus vectors JF bioRxiv FD Cold Spring Harbor Laboratory SP 328310 DO 10.1101/328310 A1 Rajvinder Karda A1 Ahad A. Rahim A1 Andrew M.S. Wong A1 Natalie Suff A1 Juan Antinao Diaz A1 Dany P. Perocheau A1 Nuria Palomar Martin A1 Michael Hughes A1 Juliette M.K.M. Delhove A1 John R. Counsell A1 Jonathan D. Cooper A1 Els Henckaerts A1 Tristan R. Mckay A1 Suzanne M.K. Buckley A1 Simon N. Waddington YR 2018 UL http://biorxiv.org/content/early/2018/05/22/328310.abstract AB 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.To further restrict biosensor activity to the CNS, we performed intracerebroventricular injection of each vector. We observed greater restriction of bioluminescence to the head and spine with both vectors. Immunohistochemistry revealed strongest expression in cells of neuronal morphology. LPS administration stimulated a 4-fold increase over baseline bioluminescence.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 using a model of LPS-induced inflammation. This technology employs the 3R’s of biomedical animal research, complements existing germline-transgenic models and may be applicable to other rodent disease models with the use of different response elements.