Altered emotional and locomotor responses in mice deficient in the transcription factor CREM

Various transcription factors act as nuclear effecters of the cAMP-dependen t signaling pathway. These are the products of three genes in the mouse, CR EB, CRE modulator (CREM), and ATF-1. CREM proteins are thought to play impo rtant roles within the hypothalamic-pituitary axis and in the control of rh ythmic functions in the pineal gland. We have generated CREM-mutant mice an d investigated their response in a variety of behavioral tests. CREM-null m ice show a drastic increase in locomotion. In contrast to normal mice, the CREM-deficient mice show equal locomotor activity during the circadian cycl e. The anatomy of the hypothalamic suprachiasmatic nuclei, the center of th e endogenous pacemaker, is normal in mutant mice. Remarkably, CREM mutant m ice also elicit a different emotional state, revealed by a lower anxiety in two different behavioral models, but they preserve the conditioned reactiv eness to stress. These results demonstrate the high degree of functional sp ecificity of each cAMP-responsive transcription factor in behavioral contro l.