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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F21%3A00543858" target="_blank" >RIV/67985823:_____/21:00543858 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1371/journal.pcbi.1008987" target="_blank" >https://doi.org/10.1371/journal.pcbi.1008987</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pcbi.1008987" target="_blank" >10.1371/journal.pcbi.1008987</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

<a href="/cs/project/GA19-01845S" target="_blank" >GA19-01845S: Identifikace rytmických mateřských signálů pomocí analýzy cirkadiánního trankriptomu a proteomu ve fetálních suprachiasmatických jádrech</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

PLoS Computational Biology

ISSN

1553-734X

e-ISSN

1553-7358

Svazek periodika

17

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

31

Strana od-do

e1008987

Kód UT WoS článku

000664322500003

EID výsledku v databázi Scopus

2-s2.0-85106969563