THE CIRCADIAN SYSTEM OF C-FOS DEFICIENT MICE

We examined the role of c-fos in the synchronization of circadian rhyt hms to environmental light cycles using a line of gene-targeted mice c arrying a null mutation at this locus. Circadian locomotor rhythms in mutants had similar periods as wild-type controls but took significant ly longer than controls to entrain to 12:12 light-dark cycles. Light-i nduced phase shifts of rhythms in constant dark were attenuated in mut ants although the circadian timing of phase delays and advances was no t changed. A functional retinohypothalamic projection was indicated fr om behavioral results and light-induced jun-B expression in the SCN. T he results indicate that while c-fos activation is not an absolute req uirement for rhythm generation nor photic responses, it is required fo r normal entrainment of the mammalian biological clock.