Tamoxifen in the Mouse Brain: Implications for Fate-Mapping Studies Using the Tamoxifen-Inducible Cre-loxP System

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F16%3A00469033" target="_blank" >RIV/68378041:_____/16:00469033 - isvavai.cz</a>

Alternative codes found

RIV/61388971:_____/16:00469033 RIV/00216208:11130/16:10332513

Result on the web

<a href="http://dx.doi.org/10.3339/fncel.2016.00243" target="_blank" >http://dx.doi.org/10.3339/fncel.2016.00243</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3339/fncel.2016.00243" target="_blank" >10.3339/fncel.2016.00243</a>

Result language

angličtina

Original language name

Tamoxifen in the Mouse Brain: Implications for Fate-Mapping Studies Using the Tamoxifen-Inducible Cre-loxP System

Original language description

The tamoxifen (TX)-inducible Cre-loxP system is used to overcome gene targeting pre-adult lethality, to modify a specific cell population at desired time, and to visualize cells in fate-mapping studies. Here we focused on TX degradation, because for fate-mapping studies, the period during which TX or its metabolites remain in the CNS, is essential. Additionally, we aimed to define the TX administration scheme enabling the maximal recombination together with minimal animal mortality. The time window between TX injection and the start of experiments should be large enough to allow complete degradation of TX and its metabolites. Otherwise, these substances could promote an undesired recombination, leading to data misinterpretation. We defined the time window, allowing the complete degradation of TX and its metabolites in the mouse brain after i.p. TX injection. We determined the activity of TX and its metabolites in vitro, and a minimal effective concentration of the most potent metabolite 4-OH-TX causing recombination in vivo. For this purpose, we analyzed the recombination rate in NG2-tdTomato mice, in which TX administration triggers the expression of red fluorescent protein in NG2-expressing cells, and employed a liquid chromatography- mass spectrometry, to determine the concentration of studied substances in the brain. Our results showed that TX and its metabolites were degraded within 8 days in young C57BL/6J mice, while the age-matched FVB mice displayed more effective degradation. Moreover, aged C57BL/6J mice were unable to metabolize all substances within 8 days. The lowering of initial TX dose leads to a significantly faster degradation of all studied substances. A disruption of the blood-brain barrier caused no concentration changes of any TX metabolites in the ipsilateral hemisphere. Taken together, we showed that TX metabolism in mouse brains is age-, strain- and dose-dependent, and these factors should be taken into account in the experimental design.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FH - Neurology, neuro-surgery, nuero-sciences

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

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

Name of the periodical

Frontiers in Cellular Neuroscience

ISSN

1662-5102

e-ISSN

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Volume of the periodical

10

Issue of the periodical within the volume

ost

Country of publishing house

CH - SWITZERLAND

Number of pages

12

Pages from-to

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UT code for WoS article

000385762900001

EID of the result in the Scopus database

2-s2.0-84992529991