Journal of biological rhythmsAug 28, 2019

Limits of Two Common Genetic Mouse Models for Studying Biological Clocks

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 21, 2026

Abstract

Neuropeptide expression in the Avp-IRES2-Cre and Vip-IRES-Cre mouse strains is significantly decreased due to the insertion of an IRES(2)-Cre cassette.

The suprachiasmatic nucleus (SCN) regulates circadian rhythms by expressing neuropeptides that synchronize bodily clocks.
Arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) are important neuropeptides produced by specific neuron subpopulations in the SCN.
The Avp-IRES2-Cre and Vip-IRES-Cre mouse strains are designed to study these AVP- and VIP-expressing neurons through targeted genetic manipulation.
Insertion of the IRES(2)-Cre cassette into neuropeptide-encoding genes significantly reduces their expression.
This reduction in neuropeptide expression could confound experimental outcomes, necessitating careful consideration in research using these mouse models.

Simplified

The principal circadian pacemaker in mammals, the suprachiasmatic nucleus (SCN), expresses a number of neuropeptides that facilitate intercellular synchrony, helping to generate coherent outputs to peripheral clocks throughout the body. In particular, arginine vasopressin (AVP)- and vasoactive intestinal peptide (VIP)-expressing neurons have been recognized as crucial subpopulations within the SCN and have thus been the focus of many chronobiological studies. Here, we analyze the neuropeptide expression of 2 popular transgenic mouse strains commonly used to direct or restrict Cre-mediated recombination to AVP- and VIP-ergic neurons. The Avp-IRES2-Cre (JAX #023530) and Vip-IRES-Cre (JAX #010908) "driver" mouse strains express the Cre recombinase under the control of the endogenousorgene, respectively, allowing scientists either to ablate their gene of interest or to overexpress a transgene in a cell type-specific manner. Although these are potentially very powerful tools for chronobiologists and other scientists studying AVP- and VIP-ergic neurons, we found that neuropeptide expression in these mice is significantly decreased when an IRES(2)-Cre cassette is inserted downstream of the neuropeptide-encoding gene locus. The impact of IRES(2)-Cre cassette insertion on neuropeptide expression may be a confounding factor in many experimental designs. Our findings suggest that extreme caution must be exercised when using these mouse models to avoid misinterpretation of empirical results. Avp Vip

Full Text

Full text is available at the source.

View Full Text ↗

Limits of Two Common Genetic Mouse Models for Studying Biological Clocks

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief