SOMABIO · Easy and rapid generation of light-emitting somatic-transgenic mice to monitor specific disease states and to screen effective drugs

For decades, researchers have used small mammals to study the underlying processes of human disease and potential therapies for such ailments. Current strategies for measuring disease progression and/or drug effect usually involve groups of animals being killed at multiple time points for post-mortem tissue analysis. Recently, transgenic strains of mice have been created in which light-emitting luciferase is produced when a disease-specific pathway is switched on or off. High-sensitivity cameras are used to follow the profile of light emission in individual animals during disease induction/treatment, thus avoiding serial culling. However generation of transgenic mice is time-consuming, expensive, and costly in terms of animal usage. A major problem is that every tissue in the mouse may emit light, soorgan-specific effects are difficult to discern. This research programme describes the development of a process of generating light-emitting somatic-transgenic rodents by gene transfer in neonates or in utero. This permits the production of micecontaining bespoke biosensors and avoids the lengthy process of production of germline transgenics. Crucially, specific organs and tissues can be targeted by the appropriate choice of application route and gene transfer vector. This technique is highly adaptable to new developments in biology (for example, new signalling targets, new genetic regulators such as miRNA and improved light-emitting enzymes) and is applicable to any strain of mouse or rat. As proof-of concept several widely-used models of disease will be examined over the duration of this programme of work: i) LPS-induced lung inflammation ii) Bleomycin-induced lung fibrosis iii) LPS-induced liver inflammation iv) Carbon tetrachloride/ethanol-induced liver fibrosis v) collagen-induced arthritis vi) Cutaneous wound-healing following dorsal punch biopsy vii) Neonatal cerebral hypoxia/ischaemia