Circadian locomotor rhythms in mice with targeted disruption of the gene for the carbon monoxide synthesizing enzyme, heme oxygenase-2

Carbon monoxide (CO), generated in neurons by the enzyme heme oxygenase-2 ( HO2), is postulated to be a gaseous signaling molecule in the mammalian bra in. Because of the recent evidence suggesting an important role of another endogenously produced gas, nitric oxide (NO), in entrainment of circadian r hythms in mammals, we hypothesized that CO may also be involved in regulati ng these rhythms. Consistent with this idea, others have found a circadian rhythm of heme turnover and CO synthesis can be induced by bright light. Fu rthermore, HO2 is co-localized with guanylyl cyclase, the putative target o f CO, throughout the brain, with high amounts of staining in the suprachias matic nucleus (SCN) of the hypothalamus. The goal of the present study was to evaluate the role of CO in photic entrainment in wild-type and HO2 defic ient mice; HO2-/- mice did not display any abnormalities in circadian rhyth micity. Entrainment to a light-dark cycle, the ability to phase delay locom otor activity after a four hour phase shift in photoperiod, and the period of the free running rhythm (tau) were similar between HO2-/- and wild-type mice. Taken together, these data suggest that CO does not play a major role in regulating circadian activity rhythms in mice.