Androgens, required for normal development and fertility of males and females, have vital roles in the reproductive
tract, brain, cardiovascular system, smooth muscle and bone. Androgens function via the androgen receptor (AR), a
ligand-dependent transcription factor. To assay and localise AR activity in vivo we generated the transgenic “ARELuc”
mouse, expressing a luciferase reporter gene under the control of activated endogenous AR. In vivo imaging of
androgen-mediated luciferase activity revealed several strongly expressing tissues in the male mouse as expected
and also in certain female tissues. In males the testes, prostate, seminal vesicles and bone marrow all showed high
AR activity. In females, strong activity was seen in the ovaries, uterus, omentum tissue and mammary glands. In both
sexes AR expression and activity was also found in salivary glands, the eye (and associated glands), adipose tissue,
spleen and, notably, regions of the brain. Luciferase protein expression was found in the same cell layers as
androgen receptor expression. Additionally, mouse AR expression and activity correlated well with AR expression in
human tissues. The anti-androgen bicalutamide reduced luciferase signal in all tissues. Our model demonstrates that
androgens can act in these tissues directly via AR, rather than exclusively via androgen aromatisation to estrogens
and activation of the estrogen receptor. Additionally, it visually demonstrates the fundamental importance of AR
signalling outside the normal role in the reproductive organs. This model represents an important tool for
physiological and developmental analysis of androgen signalling, and for characterization of known and novel
androgenic or antiandrogenic compounds.