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In Vivo Monitoring of Circadian Clock Gene Expression in the Mouse Suprachiasmatic Nucleus Using Fluorescence Reporters
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Reduced VIP Expression Affects Circadian Clock Function in VIP-IRES-CRE Mice (JAX 010908)
Deborah A M Joye1, Kayla E Rohr1, Danielle Keller1
1Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin.
Journal of Biological Rhythms
|May 29, 2020
Summary
The VIP-IRES-Cre transgene reduces vasoactive intestinal polypeptide (VIP) expression, impacting circadian rhythms. However, arginine vasopressin signaling compensates, sustaining suprachiasmatic nucleus (SCN) function and daily timekeeping.
Area of Science:
- Neuroscience
- Chronobiology
- Molecular Biology
Background:
- Circadian rhythms are governed by the suprachiasmatic nucleus (SCN), utilizing neuropeptide signaling for daily timekeeping.
- Vasoactive intestinal polypeptide (VIP) is crucial for SCN function, but its specific role in SCN circuits remains unclear.
Purpose of the Study:
- To investigate the precise role of VIP neurons in SCN circuits using the VIP-IRES-Cre mouse model.
- To determine the impact of manipulating VIP neurons on circadian rhythmicity and SCN function.
Main Methods:
- Utilized VIP-IRES-Cre transgenic mice to specifically manipulate VIP neurons.
- Assessed circadian phenotypes including reentrainment, free-running period, and molecular rhythms (PER2::LUC) in constant darkness.
- Investigated the role of neuropeptide signaling, including arginine vasopressin, in sustaining SCN function.
Main Results:
- VIP-IRES-Cre transgene significantly reduces VIP expression in heterozygous and homozygous mice.
- Homozygous VIP-Cre mice exhibit altered circadian rhythms, including faster reentrainment and shorter periods, but maintain rhythmicity.
- Arginine vasopressin signaling, not residual VIP, sustains molecular rhythms and SCN function in VIP-Cre mice.
Conclusions:
- The VIP-IRES-Cre transgene interferes with VIP expression, necessitating careful interpretation of results from this model.
- Loss of VIP signaling can be compensated by other neuropeptides, such as arginine vasopressin, to maintain SCN function.
- This study provides novel insights into the neuropeptide mechanisms underlying daily timekeeping in the SCN master clock.
Keywords:
VIP-IRES-CRE mice (JAX 010908)arginine vasopressincircadiancre transgeneneuropeptidessuprachiasmatic nucleusvasoactive intestinal polypeptideMore Related Videos
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