Development of a new flippase-dependent mouse model for red fluorescence-based isolation of KRAS-G12D oncogene-expressing tumor cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F25%3A00635731" target="_blank" >RIV/68378050:_____/25:00635731 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s11248-024-00429-2?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=scopus" target="_blank" >https://link.springer.com/article/10.1007/s11248-024-00429-2?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=scopus</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s11248-024-00429-2" target="_blank" >10.1007/s11248-024-00429-2</a>
Alternative languages
Result language
angličtina
Original language name
Development of a new flippase-dependent mouse model for red fluorescence-based isolation of KRAS-G12D oncogene-expressing tumor cells
Original language description
Proto-oncogene KRAS, GTPase (KRAS) is one of the most intensively studied oncogenes in cancer research. Although several mouse models allow for regulated expression of mutant KRAS, selective isolation and analysis of transforming or tumor cells that produce the KRAS oncogene remains a challenge. In our study, we present a knock-in model of oncogenic variant KRASG12D that enables the ,,activation,, of KRASG12D expression together with production of red fluorescent protein tdTomato. Both proteins are expressed from the endogenous Kras locus after recombination of a transcriptional stop box in the genomic DNA by the enzyme flippase (Flp). We have demonstrated the functionality of the allele termed RedRas (abbreviated KrasRR) under in vitro conditions with mouse embryonic fibroblasts and organoids and in vivo in the lung and colon epithelium. After recombination with adenoviral vectors carrying the Flp gene, the KrasRR allele itself triggers formation of lung adenomas. In the colon epithelium, it causes the progression of adenomas that are triggered by the loss of tumor suppressor adenomatous polyposis coli (APC). Importantly, cells in which recombination has successfully occurred can be visualized and isolated using the fluorescence emitted by tdTomato. Furthermore, we show that KRASG12D production enables intestinal organoid growth independent of epidermal growth factor (EGF) signaling and that the KRASG12D function is effectively suppressed by specific inhibitor MRTX1133.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
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
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Transgenic Research
ISSN
0962-8819
e-ISSN
1573-9368
Volume of the periodical
34
Issue of the periodical within the volume
1
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
19
Pages from-to
9
UT code for WoS article
001393523100004
EID of the result in the Scopus database
2-s2.0-85214865148