Many biochemical, physiological, and behavioral processes display daily rhythms 
generated by an internal timekeeping mechanism referred to as the circadian 
clock. The core oscillator driving this clock is located in the ventral part of 
the hypothalamus, the so called suprachiasmatic nuclei (SCN). At the molecular 
level, this oscillator is thought to be composed of interlocking autoregulatory 
feedback loops involving a set of clock genes. Among the components driving the 
mammalian circadian clock are the Period 1 and 2 (mPer1 and mPer2) and 
Cryptochrome 1 and 2 (mCry1 and mCry2) genes. A mutation in the mPer2 gene leads 
to a gradual loss of circadian rhythmicity in mice kept in constant darkness 
(DD). Here we show that inactivation of the mCry2 gene in mPer2 mutant mice 
restores circadian rhythmicity and normal clock gene expression patterns. Thus, 
mCry2 can act as a nonallelic suppressor of mPer2, which points to direct or 
indirect interactions of PER2 and CRY2 proteins. In marked contrast, 
inactivation of mCry1 in mPer2 mutant mice does not restore circadian 
rhythmicity but instead results in complete behavioral arrhythmicity in DD, 
indicating different effects of mCry1 and mCry2 in the clock mechanism