Targeted modification of the Per2 clock gene alters circadian function in mPer2(luciferase) (mPer2(Luc)) mice

0543858 - FGÚ 2022 RIV US eng J - Journal Article
Ralph, M. R. - Shi, S.-Q. - Johnson, C. H. - Houdek, Pavel - Shrestha, T. C. - Crosby, P. - O´Neill, J. S. - Sládek, Martin - Stinchcombe, A. R. - Sumová, Alena
Targeted modification of the Per2 clock gene alters circadian function in mPer2(luciferase) (mPer2(Luc)) mice.
PLoS Computational Biology. Roč. 17, č. 5 (2021), č. článku e1008987. ISSN 1553-734X. E-ISSN 1553-7358
R&D Projects: GA ČR(CZ) GA19-01845S
Institutional support: RVO:67985823
Keywords : circadian clock * mPer2Luc mouse * circadian reporter * suprachiasmatic nuclei * circadian entrainment
OECD category: Physiology (including cytology)
Impact factor: 4.779, year: 2021
Method of publishing: Open access
https://doi.org/10.1371/journal.pcbi.1008987

Modification of the Per2 clock gene in mPer2(Luc) reporter mice significantly alters circadian function. Behavioral period in constant dark is lengthened, and dissociates into two distinct components in constant light. Rhythms exhibit increased bimodality, enhanced phase resetting to light pulses, and altered entrainment to scheduled feeding. Mechanistic mathematical modelling predicts that enhanced protein interactions with the modified mPER2 C-terminus, combined with differential clock regulation among SCN subregions, can account for effects on circadian behavior via increased Per2 transcript and protein stability. PER2::LUC produces greater suppression of CLOCK:BMAL1 E-box activity than PER2. mPer2(Luc) carries a 72 bp deletion in exon 23 of Per2, and retains a neomycin resistance cassette that affects rhythm amplitude but not period. The results show that mPer2(Luc) acts as a circadian clock mutation illustrating a need for detailed assessment of potential impacts of c-terminal tags in genetically modified animal models.
Permanent Link: http://hdl.handle.net/11104/0320972