Mice hemizygous for the transgenic insert are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These transgenic mice express luciferase in response to activation of the Smad2/3-dependent signaling pathway. Cultured primary astrocytes isolated from transgenic mice exhibited luciferase activity when stimulated with TGF-beta. Higher treatment levels of activin and nodal elicited similar luciferase activity. Lipopolysaccharide (LPS) challenge results in strong bioluminescence emissions from the intestinal region and brain. Mechanical injury to the neocortex results in an increase of bioluminescence in 2 hours, which peaks at 4 hours and returns to baseline approximately 48 hours after the injury. Biochemical assays for luciferase activity correlated with noninvasive bioluminescence imaging analysis. This mutant mouse strain may be useful in studies of the role of transforming growth factor beta in intracellular signaling with noninvasive in vivo imaging.