1. Department of Molecular and Human Genetics Houston, Texas 77030, USA
2. Division of Neuroscience Houston, Texas 77030, USA
3. Verna and Marrs McLean Department of Biochemistry Houston, Texas 77030, USA
4. Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
5. Present address: Max Planck Institute for Experimental Endocrinology, Feodor-Lynen-Strasse 7, 30625 Hanover, Germany.

Correspondence to: Cheng Chi Lee¹ Correspondence and requests for materials should be addressed to C.C.L. (e-mail: Email: ching@bcm.tmc.edu)

Circadian rhythms are driven by endogenous biological clocks that regulate many biochemical, physiological and behavioural processes in a wide range of life forms¹. In mammals, there is a master circadian clock in the suprachiasmatic nucleus of the anterior hypothalamus. Three putative mammalian homologues (mPer1, mPer2 and mPer3) of the Drosophila circadian clock gene period (per) have been identified²,³,⁴,⁵,⁶,⁷,⁸. The mPer genes share a conserved PAS domain (a dimerization domain found in Per, Arnt and Sim) and show a circadian expression pattern in the suprachiasmatic nucleus. To assess the in vivo function of mPer2, we generated and characterized a deletion mutation in the PAS domain of the mouse mPer2 gene. Here we show that mice homozygous for this mutation display a shorter circadian period followed by a loss of circadian rhythmicity in constant darkness. The mutation also diminishes the oscillating expression of both mPer1 and mPer2 in the suprachiasmatic nucleus, indicating that mPer2 may regulate mPer1in vivo. These data provide evidence that an mPer gene functions in the circadian clock, and define mPer2 as a component of the mammalian circadian oscillator.