Inhibitor of DNA binding 2 (Id2) Regulates Photic Entrainment Responses in Mice: Differential Responses of the Id2-/- Mouse Circadian System Are Dependent on Circadian Phase and on Duration and Intensity of Light

Author:

Duffield Giles E.12ORCID,Han Sung3,Hou Tim Y.1,de la Iglesia Horacio O.3,McDonald Kathleen A.1,Mecklenburg Kirk L.4,Robles-Murguia Maricela12

Affiliation:

1. Department of Biological Sciences, Galvin Life Science Center, University of Notre Dame, Notre Dame, Indiana

2. Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana

3. Department of Biology and Graduate Program in Neuroscience, University of Washington, Seattle, Washington

4. Department of Biology, Indiana University South Bend, South Bend, Indiana

Abstract

ID2 is a rhythmically expressed helix–loop–helix transcriptional repressor, and its deletion results in abnormal properties of photoentrainment. By examining parametric and nonparametric models of entrainment, we have started to explore the mechanism underlying this circadian phenotype. Id2-/- mice were exposed to differing photoperiods, and the phase angle of entrainment under short days was delayed 2 h as compared with controls. When exposed to long durations of continuous light, enhanced entrainment responses were observed after a delay of the clock but not with phase advances. However, the magnitude of phase shifts was not different in Id2-/- mice tested in constant darkness using a discrete pulse of saturating light. No differences were observed in the speed of clock resetting when challenged by a series of discrete pulses interspaced by varying time intervals. A photic phase-response curve was constructed, although no genotypic differences were observed. Although phase shifts produced by discrete saturating light pulses at CT16 were similar, treatment with a subsaturating pulse revealed a ~2-fold increase in the magnitude of the Id2-/- shift. A corresponding elevation of light-induced per1 expression was observed in the Id2-/- suprachiasmatic nucleus (SCN). To test whether the phenotype is based on a sensitivity change at the level of the retina, pupil constriction responses were measured. No differences were observed in responses or in retinal histology, suggesting that the phenotype occurs downstream of the retina and retinal hypothalamic tract. To test whether the phenotype is due to a reduced amplitude of state variables of the clock, the expression of clock genes per1 and per2 was assessed in vivo and in SCN tissue explants. Amplitude, phase, and period length were normal in Id2-/- mice. These findings suggest that ID2 contributes to a photoregulatory mechanism at the level of the SCN central pacemaker through control of the photic induction of negative elements of the clock.

Funder

National Institute of Neurological Disorders and Stroke

National Institute of General Medical Sciences

Publisher

SAGE Publications

Subject

Physiology (medical),Physiology

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Photic Entrainment of the Circadian System;International Journal of Molecular Sciences;2022-01-10

2. Targeted Disruption of the Inhibitor of DNA Binding 4 (Id4) Gene Alters Photic Entrainment of the Circadian Clock;International Journal of Molecular Sciences;2021-09-06

3. Meta-analysis of light and circadian timekeeping in rodents;Neuroscience & Biobehavioral Reviews;2021-04

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