Early doors (Edo) mutant mouse reveals the importance of period 2 (PER2) PAS domain structure for circadian pacemaking

The circadian clock of Per2(Edo/Edo) mice is accelerated by 1.5 hours.

• A novel mutation in the PER2 protein, referred to as early doors (Edo), affects the dimerization region of the PAS domain.
• Structural analyses indicate that the Edo mutation alters the packing of the interdomain linker in the PER2 protein.
• PER2(Edo) complexes with clock proteins but has increased vulnerability to degradation by casein kinase 1ε.
• Per2(Edo/Edo); Csnk1e(Tau/Tau) mice exhibit robust circadian rhythms of less than 19 hours.
• These findings highlight a direct causal link between the structure of the PER2 protein and the timing mechanisms of the suprachiasmatic nucleus.

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