Reduced VIP Expression Affects Circadian Clock Function in VIP-IRES-CRE Mice (JAX 010908).
VIP-IRES-CRE mice (JAX 010908)
arginine vasopressin
circadian
cre transgene
neuropeptides
suprachiasmatic nucleus
vasoactive intestinal polypeptide
Journal
Journal of biological rhythms
ISSN: 1552-4531
Titre abrégé: J Biol Rhythms
Pays: United States
ID NLM: 8700115
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
pubmed:
29
5
2020
medline:
8
6
2021
entrez:
29
5
2020
Statut:
ppublish
Résumé
Circadian rhythms are programmed by the suprachiasmatic nucleus (SCN), which relies on neuropeptide signaling to maintain daily timekeeping. Vasoactive intestinal polypeptide (VIP) is critical for SCN function, but the precise role of VIP neurons in SCN circuits is not fully established. To interrogate their contribution to SCN circuits, VIP neurons can be manipulated specifically using the DNA-editing enzyme Cre recombinase. Although the Cre transgene is assumed to be inert by itself, we find that VIP expression is reduced in both heterozygous and homozygous adult VIP-IRES-Cre mice (JAX 010908). Compared with wild-type mice, homozygous VIP-Cre mice display faster reentrainment and shorter free-running period but do not become arrhythmic in constant darkness. Consistent with this phenotype, homozygous VIP-Cre mice display intact SCN PER2::LUC rhythms, albeit with altered period and network organization. We present evidence that the ability to sustain molecular rhythms in the VIP-Cre SCN is not due to residual VIP signaling; rather, arginine vasopressin signaling helps to sustain SCN function at both intracellular and intercellular levels in this model. This work establishes that the VIP-IRES-Cre transgene interferes with VIP expression but that loss of VIP can be mitigated by other neuropeptide signals to help sustain SCN function. Our findings have implications for studies employing this transgenic model and provide novel insight into neuropeptide signals that sustain daily timekeeping in the master clock.
Identifiants
pubmed: 32460660
doi: 10.1177/0748730420925573
pmc: PMC9235543
mid: NIHMS1816731
doi:
Substances chimiques
Neuropeptides
0
Period Circadian Proteins
0
Vasoactive Intestinal Peptide
37221-79-7
Cre recombinase
EC 2.7.7.-
Integrases
EC 2.7.7.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
340-352Subventions
Organisme : NINDS NIH HHS
ID : R01 NS091234
Pays : United States
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