Limitations of the Avp-IRES2-Cre (JAX #023530) and Vip-IRES-Cre (JAX #010908) Models for Chronobiological Investigations

J Biol Rhythms. 2019 Dec;34(6):634-644. doi: 10.1177/0748730419871184. Epub 2019 Aug 27.

Abstract

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 endogenous Avp or Vip gene, 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.

Keywords: AVP; VIP; mouse models; neuropeptide expression; suprachiasmatic nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine Vasopressin / genetics*
  • Chronobiology Phenomena
  • Circadian Clocks*
  • Circadian Rhythm
  • Female
  • Gene Expression*
  • Integrases / genetics
  • Male
  • Mice
  • Mice, Transgenic*
  • Neurons / physiology
  • Suprachiasmatic Nucleus / cytology
  • Suprachiasmatic Nucleus / physiology
  • Vasoactive Intestinal Peptide / genetics*

Substances

  • Arginine Vasopressin
  • Vasoactive Intestinal Peptide
  • Cre recombinase
  • Integrases

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