Altered behavioral rhythms and clock gene expression in mice with a targeted mutation in the Period1 gene

A group of specialized genes has been defined to govern the molecular mecha nisms controlling the circadian clock in mammals. Their expression and the interactions among their products dictate circadian rhythmicity. Three gene s homologous to Drosophila period exist in the mouse and are thought to be major players in the biological clock. Here we present the generation of mi ce in which the founding member of the family, Per1, has been inactivated b y homologous recombination. These mice present rhythmicity in locomotor act ivity, but with a period almost 1 h shorter than wild-type littermates. Mor eover, the expression of clock genes in peripheral tissues appears to be de layed in Per1 mutant animals. Importantly, light-induced phase shifting app ears conserved. The oscillatory expression of clock genes and the induction of immediate-early genes in response to light in the master clock structur e, the suprachiasmatic nucleus, are unaffected. Altogether, these data demo nstrate that Per] plays a distinct role within the Per family, as it may be involved predominantly in peripheral clocks and/or in the output pathways of the circadian clock.