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Characterization of the Circadian System of NGFI-A and NGFI-A/NGFI-B Deficient Mice

C. Vugrinic

Center for Sleep and Circadian Neurobiology, Departments of Biological Sciences and Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305

S. L. Lee

J. D. Milbrandt

Department of Pathology, Washington University, St. Louis, MO 63110

J. D. Mikkelsen

Department of Neurobiology, H. Lundbeck A/S, Valby, Denmark

B. F. O'Hara

H. C. Heller

Center for Sleep and Circadian Neurobiology, Departments of Biological Sciences and Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305

The genes NGFI-A (also known as EGR-1, zif/268, and Krox-24) and NGFI-B (nur/77) have previously been shown to be induced in the SCN of rats and hamsters by photic stimulation during the subjective night. The purpose of this study is to determine whether these genes are also induced in the SCN of mice and, if so, to characterize the circadian system of animals in which either NGFI-A or both NGFI-A and NGFI-B were eliminated by homologous recombination. In wildtype mice, NGFI-A mRNA was found to be induced in the SCN as in other rodent species. Therefore, wheel-running activity was recorded from null mutants and wildtype controls under LD 12:12 and DD conditions. Mice of all three strains appeared to entrain normally to LD 12:12 and could re-entrain to both phase advances and phase delays of the light cycle. The response of the circadian pacemaker of all three genotypes to acute light pulses appeared to be normal. The retinal innervation of the SCN in NGFI-A-/- mice and the photic induction of Fos in the SCN of both NGFI-A-/- and NGFI-A-/-B-/- mice were indistinguishable from wildtype mice. These results indicate that induction of NGFI-A and NGFI-B is not required for photic entrainment or phase shifting of the mouse circadian system.

Key Words: NGFI-A • NGFI-B • immediate early genes • circadian • locomotor activity • phase shifting • entrainment

Journal of Biological Rhythms, Vol. 13, No. 4, 347-357 (1998)
DOI: 10.1177/074873098129000174


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