Dual-color luciferase mouse directly demonstrates coupled expression of two clock genes

We have established a dual-color transgenic mouse that simultaneously reports the expression of two clock genes, Bmal1 and Per2, in a single tissue. The expression of the two genes is monitored with green- and red-emitting beetle luciferases with a single luminescent substrate. Antiphasic oscillations of Bmal1 and Per2, consistent with their endogenous mRNA profiles, were clearly monitored in the suprachiasmatic nucleus (SCN), the master circadian pacemaker, and in the peripheral tissues, demonstrating that the system allows the long-term, quantitative, and simultaneous monitoring of the expression of the two genes. We also showed that although the expression patterns of Bmal1 and Per2 in each organ are strictly antiphasic, the recorded circadian phases and periods of both genes varied between organs. The phase shifts in the expression of both genes in the SCN, induced by a change of medium, also occurred in a similar manner. Therefore, this dual-color luciferase mouse allows noninvasive and continuous monitoring of the coupled expression of two clock genes. This system provides a simple technique with which to unravel the complex interactions of two genes in the body.